Progress 10/01/15 to 09/30/16
Outputs
Progress Report Objectives (from AD-416): Objective 1: Determine the impact of variant and emerging viruses on the development and control of respiratory disease in ruminants. Develop means to detect and survey for variant viruses and develop models for evaluating infections with emerging variant viruses. Subobjectives: (1a) Determine impact of variant and emerging viruses; (1b) Improve current surveillance methods and diagnostic tools used to detect and control emerging viruses. Objective 2: Elucidate the host-pathogen interactions associated with the Bovine Respiratory Disease Complex (BRDC) by defining host pathways modulated as a result of viral infections and characterizing the role of stress and immunological related host effector molecules in BRDC. Subobjectives: (2a) Define interactions of viral pathogens that may contribute to the development of respiratory disease; (2b) Define modulation of host immune response to viral infection associated with stress caused by vitamin D insufficiency. Objective 3: Evaluate formulations and delivery systems for vaccination of neonates by identifying means to modulate stress and immunological factors associated with BRDC. Generate identification criteria and means to generate �vaccine ready� calves to develop intervention strategies for controlling viral respiratory infections of ruminants. Subobjectives: (3a) Identify factors, associated with common management practices, that modulate immune function in neonatal calves; (3b) Evaluate candidate vaccine for use in calves. Approach (from AD-416): The goal of this project is to reduce the incidence and impact of viral infections in ruminants with particular emphasis on viral infections that contribute to respiratory disease in cattle. The project encompasses three distinct but interrelated research efforts. The first is to determine the incidence and impact of variant viruses, such as subgenotypes of bovine viral diarrhea virus (BVDV), and emerging viruses, such as HoBi-like viruses, to bovine respiratory disease. The purpose of this research is to determine if new antigens, representing variant and emerging viruses, need to be included in vaccines. The second is to examine the interaction of host and virus in respiratory disease. Included in this effort will be the study of host immune dysfunction, resulting from viral infection, nutrition, or stress. The purpose of this research is to define factors that contribute to respiratory disease in order to develop means of intervention that negate or ameliorate those factors. The third is to determine means by which host resistance to viral infection can be enhanced with emphasis on improving protective innate and acquired immune responses in calves. The information generated from these three research areas will be used in the development of intervention strategies to control and eliminate viral pathogens. Improved control of viral pathogens will benefit consumers by ensuring a healthful food supply, enhance animal health and well-being, and reduce production costs for farmers and ranchers. This is the final report for the project 5030-32000-106-00D terminating September 30, 2016. The goal of this project is to reduce viral infections in ruminants that contribute to respiratory disease in cattle. Known viruses associated with bovine respiratory disease complex (BRDC) include bovine viral diarrhea viruses (BVDV), infectious bovine rhinotracheitis virus (IBR), bovine respiratory syncytial virus (BRSV), bovine parainfluenza virus 3 (BPI3V) and bovine coronavirus (BoCV). Emerging viruses include a pestivirus variously referred to as HoBi-like virus, atypical bovine pestivirus or BPI3V3 found infecting cattle in South America, Asia, Southeast Asia and Europe. Substantial progress has been made on each of the three objectives of this research as detailed below. Supporting Objective 1, there were three different areas of research conducted under this objective. One area of research addressed the detection and characterization of viruses associated with respiratory disease in cattle (bovine respiratory disease or BRD). In a collaborative study samples were collected from feedlot cattle suffering from BRD and tested for the presence of bovine herpesvirus-1 (BoHV-1), bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine coronaviruses (BoCV) and parainfluenza-3 virus (PI3V). The samples were tested to determine which viruses were present and in which combination. The results indicated that multiple viruses may be present in BRD cases and that multiple tests need to be used to detect all the viruses that are present. This information is important to the design of tests and vaccines to detect and control the viruses that contribute to BRD. A second area of research focused on characterizing infections with an emerging bovine pestivirus, known as HoBi-like virus. HoBi-like viruses thus far have only been isolated from animals in South America, Asia and Europe. If a bovine fetus is exposed to HoBi-like virus, they may develop a lifelong persistent infection. Persistently infected (PI) cattle are very efficient at spreading these viruses to other cattle. In order to design control programs that would keep HoBi-like viruses from spreading around the globe, it is important to determine if cattle persistently infected with HoBi-like viruses could also transmit the virus to other domestic animals. In a series of studies, sheep, goats and pigs were infected with HoBi-like viruses by direct inoculation (experimental route of infection) or by housing with calves persistently infected with HoBi- like viruses (natural route of infection). Cattle, sheep, goats and pigs all became infected, regardless of the route of infection, indicating that the introduction of HoBi-like virus into the United States could have substantial economic impact across multiple commodity groups. A third area of research focused on detection of ruminant pestiviruses in free ranging ruminant species. In the state of Nevada, domestic cattle share grass ranges with hooved wildlife species such as big horn sheep, mountain goats and mule deer. A collaborative surveillance project conducted with samples collected between 2009 to 2013, indicated that ruminant pestiviruses infection circulate among all three wildlife species listed above. Further, it appeared that infection with ruminant pestiviruses, in particular BVDV1 and BVDV2, may have contributed to die off among these species. It is probable that domestic cattle and these wildlife species transfer BVDV back and forth and that this transmission between species contributes to the maintenance of the BVDV in the environment. This information is important to the design of BVDV control programs. Supporting objective 2, research focused on different aspects of the immune response to either acute infections or persistent infections and the characterization of naturally occurring transfer RNA-derived RNA fragments (tRFs) in cattle. Parainfluenza virus 3 (PI3) viruses are found in a number of species. Researchers found that the PI3 viruses isolated from humans, cattle and blue nosed dolphins are very similar and that these viruses block antiviral mediators in respiratory cells. This may result in blunting of antiviral responses and could be associated with the development of respiratory disease in primary and mixed infections. These results provide new information that could lead to new ways to treat PI3 infections in multiple species. Bovine pestiviruses cause two types of infections, acute and persistent. Acute infections happen when animals are infected after they are born. Typically acute infections last from two to three weeks. Persistent infections (PI) happen when an animal is infected while still in the uterus. PI last for the life span of the animal. There are a number of different outcomes of PI. Some PI animals have multiple birth defects while some appear completely normal. It is not known why there is so much variation in the outcome of PI. In studies of animals persistently infected with either BVDV2 or HoBi-like viruses it was found that there was a lot of variation in the viral populations circulating in each PI animal even if they are infected with the same viral strain. These findings suggest that host factors affect the outcome of PI. That is, some animals may be genetically predispositioned to respond to PI in one way and other animals may be genetically predispositioned to respond in a different way. In addition to showing that an individual�s genetic makeup determines how they respond to PI these studies resulted in the development of a tool (also known as a metric) that can be used to compare differences in response. Using this tool could contribute to the development of means that will help animals develop better immune defenses or that will help producers to identify animals with better immune systems. Molecules circulating in live cattle, known as transfer RNA-derived RNA fragments (tRFs), have been suggested to be regulators of gene expression in mammals. Establishing the difference in type and quantity of tRFs between healthy and diseased cattle could produce information needed to understand how genes in the animal are turned on or off, and how the animal�s immune system responds to viral infection. Previously published research characterized tRFs in mice and humans. However there was not information regarding these molecules in cattle. A research project was initiated to characterize tRFs in cattle beginning with determining the type and number present in healthy cattle. Subsequent projects will look at changes in these molecules when cattle are exposed to respiratory pathogens. Supporting objective 3, research was conducted on immune damage that may accompany the use of modified live vaccine and the level of cross protection between bovine pestiviruses. Vaccination against BVDV, using modified live vaccine (MLV), is a common practice in both beef and dairy production. In a series of studies it was demonstrated that calves vaccinated with MVL exhibited both a reduction in circulating white blood cells and in the size of the thymus, a major immune organ. These studies suggest that the licensing of MLV should include analysis of the impact of vaccination on immune cells and that this information be provided to producers. This information would allow producers to adjust vaccination strategies. Cows pregnant with calf persistently infected with a bovine pestivirus to term are continually exposed to virus during the gestation of that fetus. This results in a strong immune response in the cow to the virus carried by the PI calf. Studies were conducted to determine if this strong immune response was sufficient to prevent infection following subsequent exposure to other species of bovine pestiviruses. It was found that the immune response in dams that carried a calf persistently infected with either BVDV1 or BVDV2 was not sufficient to protect against subsequent infection of a fetus with HoBi-like virus. These results indicate that cattle in the United States, where BVDV1 and BVDV2 are endemic and vaccination against BVDV1 and BVDV2 is commonly practiced, would not be protected against HoBi-like virus should it be introduced into the United States. Thus it appears that introduction of HoBi-like virus would have significant negative effects on cattle health and the agricultural industry. Accomplishments 01 BVDV1 and BVDV2 infections have been reported in U.S. cattle but not HoBi-like virus infections. Infections with HoBi-like viruses are wide spread in South America and Asia. Serological surveillance was conducted by ARS researchers in Ames, Iowa to obtain an estimation of the proportion of cattle in the contiguous United States that have been exposed to these three pestiviruses using blood samples from 2000 cattle originating throughout the contiguous United States. The results indicated exposure to BVDV1 and BVDV2 strains with little or no exposure to HoBi-like virus stains suggesting that HoBi-like viruses have not entered the United States. Despite the wide use of BVDV vaccines, one in ten cattle sampled would not be protected against BVDV- 1 or BVDV-2 infections. One in 5 animals would not be protected against HoBi-like virus indicating that the introduction of HoBi-like viruses into US cattle would have significant economic impact. This is the largest nationwide serology study for bovine pestivirus exposure conducted to date and will be used in the development of regulatory controls to prevent the entry of HoBi-like viruses into the United States. 02 Bovine leukemia virus (BLV) infections lead to major money losses for beef and dairy producers worldwide. In this study ARS researchers at Ames, Iowa tested 2000 serum samples collected from cattle across the contiguous United States for the presence of antibodies against BLV to provide an updated picture of BLV distribution. It was found that the Northeast region has the highest prevalence (54% positive) while the lowest prevalence was found in the Mountain West region (32% positive). Overall, 38.5% of the tested samples were positive. It was also found that slaughter plants that process primarily dairy animals have a higher percent of positive results (47%), than plants that primarily process beef animals (33%). This updated picture is important for monitoring the virus distribution in the country and may help toward implementing a plan to control the disease.
Impacts
(N/A)
Publications
- Casas, E., Montaldo, H.H., Nonneman, D.J., Poli, M.A. 2015. Potential contribution of genomics and biotechnology in animal production. In: Dominguez, R.N., Valverde, R.R., Rivera, S.F., Febres, O.A., Winder, M.G., Munoz T.E., editors. Livestock in Latin America and the Caribbean: Alternatives for the sustainable, inclusive and competitive production of animal-derived foods. 1st edition. Guadalajara, Mexico: Printing Arts Mexico. p. 761-788.
- Bauermann, F.V., Falkenberg, S.M., Decari, E.F., Ridpath, J.F. 2015. Experimental infection of calves, sheep, goats and pigs with HoBi-like viruses by direct inoculation or exposure to persistently infected calves. Veterinary Microbiology. 181(3-4):289-293. doi: 10.1016/j.vetmic.2015.10. 1011.
- Eberle, K.C., McGill, J.L., Reinhardt, T.A., Sacco, R.E. 2016. Parainfluenza virus 3 blocks antiviral mediators downstream of the interferon lambda receptor by modulating stat1 phosphorylation. Journal of Virology. 90:2948-2958. doi:10.1128/JVI.02502-15.
- Casas, E., Cai, G., Neill, J.D. 2015. Characterization of circulating transfer RNA-Derived RNA fragments in cattle. Frontiers in Genetics. 6:271. doi: 10.3389/fgene.2015.00271.
- Silveria, S., Weber, M.N., Mosena, A.C., Da Silva, M.S., Streck, A.F., Pescador, C.A., Flores, E.F., Weiblen, R., Driemeier, D., Ridpath, J.F., Canal, C.W. 2015. Genetic diversity of Brazilian bovine pestiviruses detected between 1995 and 2014. Transboundary and Emerging Diseases. doi: 10.1111/tbed.12427.
- Sacco, R.E., Durbin, R.K., Durbin, J.E. 2015. Animal models of respiratory syncytial virus infection and disease. Current Opinion in Virology. 13:117- 122. doi: 10.1016/j.coviro.2015.06.003.
- Wolff, P.L., Schroeder, C., McAdoo, C., Cox, M., Nelson, D.D., Evermann, J. F., Ridpath, J.F. 2016. Evidence of bovine viral diarrhea virus infection in three species of sympatric wild ungulates in Nevada: Life history strategies may maintain endemic infections in wild populations. Frontiers in Microbiology. 7:292. doi: 10.3389/fmicb.2016.00292.
- Fulton, R.W., D'Offay, J.M., Landis, C., Miles, D.G., Smith, R.A., Saliki, J.T., Ridpath, J.F., Confer, A.W., Neill, J.D., Eberle, R., Clement, T.J., Chase, C.C., Burge, L.J., Payton, M.E. 2016. Detection and characterization of viruses as field and vaccine strains in feedlot cattle with bovine respiratory disease. Vaccine. doi: 10.1016/j.vaccine.2016.04. 020.
- McGill, J.L., Sacco, R.E. 2016. Gamma delta T cells and the immune response to respiratory syncytial virus infection. Veterinary Immunology and Immunopathology. doi: 10.1016/j.vetimm.2016.02.012.
- McGill, J.L., Rusk, R.A., Guerra-Maupome, M., Briggs, R.E., Sacco, R.E. 2016. Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with Bovine RSV and Mannheimia haemolytica. PLoS One. 11(3):e0151083. doi: 10.1371/journal.pone.0151083.
- Giammarioli, M., Ridpath, J.F., Rossi, E., Bazzucchi, M., Casciari, C., De Mia, G. 2015. Genetic detection and characterization of emerging HoBi-like viruses in archival foetal bovine serum batches. Biologicals. 43(4):220- 224. doi: 10.1016/j.biologicals.2015.05.009.
- Tait Jr, R.G., Cushman, R.A., McNeel, A.K., Casas, E., Smith, T.P., Freetly, H.C., Bennett, G.L. 2016. Estimates of epistatic and pleiotropic effects of casein alpha s1 (CSN1S1) and thyroglobulin (TG) genetic markers on beef heifer performance traits enhanced by selection. Journal of Animal Science. 94(3):920-926. doi:10.2527/jas2015-9860.
- Ridpath, J.F., Bayles, D.O., Neill, J.D., Falkenberg, S.M., Bauermann, F.F. , Holler, L., Braun, L.J., Young, D.B., Kane, S.E., Chase, C.C. 2015. Comparison of the breadth and complexity of bovine viral diarrhea (BVDV) populations circulating in 34 persistently infected cattle generated in one outbreak. Virology. 485:297-304. doi. 10.1016/j.virol.2015.07.022.
- Schaut, R.G., Ridpath, J.F., Sacco, R.E. 2016. Bovine viral diarrhea virus type 2 impairs macrophage responsiveness to toll-like receptor ligation with the exception of toll-like receptor 7. PLoS One. 11(7):e0159491. doi: 10.1371/journal.pone.0159491.
- Ferro, P.J., Fearneyhough, M., Calvert, C., Neill, J.D., Ridpath, J.F. 2016. Case Report: Emergence of bovine viral diarrhea virus persistently infected calves in a closed herd. Bovine Practitioner Journal. 50(1):28-30.
- Eberle, K.C., Neill, J.D., Venn-Watson, S.K., McGill, J.L., Sacco, R.E. 2015. Novel Atlantic bottlenose dolphin parainfluenza virus TtPIV-1 clusters with bovine PIV-3 genotype B strains. Virus Genes. 51:198-208. doi: 10.1007/s11262-015-1224-7.
- Weber, M.N., Bauermann, F.V., Bayles, D.O., Canal, C.W., Neill, J.D., Ridpath, J.F. 2016. Comparison of �HoBi�-like viral populations among persistent infected calves generated under experimental conditions and to inoculum virus. Virology. 492:225-231. doi: 10.1016/j.virol.2016.03.001.
- Flowers, E.M., Bachvaroff, T.R., Warg, J., Neill, J.D., Killian, M., Sommer Vinagre, A., Brown, S., Almeida, A., Zhan, Y., Schott, E.J. 2016. Genome sequence analysis of CsRV1: a pathogenic reovirus that infects the blue crab Callinectes sapidus across its trans-hemispheric range. Frontiers in Microbiology. 7:126. doi: 10.3389/fmicb.2016.00126.
- Ridpath, J.F., Neill, J.D. 2016. Challenges in identifying and determining the impacts of infection with pestiviruses on the herd health of free ranging cervid populations. Frontiers in Microbiology. 17(7):921. doi: 10. 3389/fmicb.2016.00921.
- Casas, E., Cai, G., Kuehn, L.A., Register, K.B., Mcdaneld, T.G., Neill, J. D. 2016. Association of microRNAs with antibody response to mycoplasma bovis in beef cattle. Animal Genetics. 11(8). doi: 10.1371/journal.pone. 0161651.
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Progress 10/01/14 to 09/30/15
Outputs
Progress Report Objectives (from AD-416): Objective 1: Determine the impact of variant and emerging viruses on the development and control of respiratory disease in ruminants. Develop means to detect and survey for variant viruses and develop models for evaluating infections with emerging variant viruses. Subobjectives: (1a) Determine impact of variant and emerging viruses; (1b) Improve current surveillance methods and diagnostic tools used to detect and control emerging viruses. Objective 2: Elucidate the host-pathogen interactions associated with the Bovine Respiratory Disease Complex (BRDC) by defining host pathways modulated as a result of viral infections and characterizing the role of stress and immunological related host effector molecules in BRDC. Subobjectives: (2a) Define interactions of viral pathogens that may contribute to the development of respiratory disease; (2b) Define modulation of host immune response to viral infection associated with stress caused by vitamin D insufficiency. Objective 3: Evaluate formulations and delivery systems for vaccination of neonates by identifying means to modulate stress and immunological factors associated with BRDC. Generate identification criteria and means to generate �vaccine ready� calves to develop intervention strategies for controlling viral respiratory infections of ruminants. Subobjectives: (3a) Identify factors, associated with common management practices, that modulate immune function in neonatal calves; (3b) Evaluate candidate vaccine for use in calves. Approach (from AD-416): The goal of this project is to reduce the incidence and impact of viral infections in ruminants with particular emphasis on viral infections that contribute to respiratory disease in cattle. The project encompasses three distinct but interrelated research efforts. The first is to determine the incidence and impact of variant viruses, such as subgenotypes of bovine viral diarrhea virus (BVDV), and emerging viruses, such as HoBi-like viruses, to bovine respiratory disease. The purpose of this research is to determine if new antigens, representing variant and emerging viruses, need to be included in vaccines. The second is to examine the interaction of host and virus in respiratory disease. Included in this effort will be the study of host immune dysfunction, resulting from viral infection, nutrition, or stress. The purpose of this research is to define factors that contribute to respiratory disease in order to develop means of intervention that negate or ameliorate those factors. The third is to determine means by which host resistance to viral infection can be enhanced with emphasis on improving protective innate and acquired immune responses in calves. The information generated from these three research areas will be used in the development of intervention strategies to control and eliminate viral pathogens. Improved control of viral pathogens will benefit consumers by ensuring a healthful food supply, enhance animal health and well-being, and reduce production costs for farmers and ranchers. The goal of this project is to reduce viral infection in ruminants that contribute to respiratory disease in cattle. Known viruses associated with bovine respiratory disease complex (BRDC) include bovine viral diarrhea viruses (BVDV), infectious bovine rhinotracheitis virus (IBR), bovine respiratory disease virus (BRSV), bovine parainfluenza virus 3 (BPI3V) and bovine coronavirus (BoCV). Emerging viruses include a pestivirus variously referred to as HoBi-like virus, atypical bovine pestivirus or BVDV3 found infecting cattle in South America, Asia, Southeast Asia and Europe. Substantial progress has been made on each of the three objectives of this research as detailed below. Supporting Objective 1, research for FY 15 concentrated on characterizing variant and emerging viruses and development of reagents that can be used to improve diagnostics and vaccines. For the past 60 years vaccines used to control BRDC have included BPI3V antigens. However, there was no information on whether the BPI3V strains, upon which the vaccines are based, are representative of the BPI3V currently in circulation. A project was initiated to generate and compare genomic sequences from field strains of BPI3V isolated over the past 30 years to vaccine and reference strains. This study demonstrated that two subgenotypes, BPI3Vb and BPI3Vc strains, previously thought to be foreign to the U.S., are currently circulating in domestic livestock herds. Based on virus neutralization using polyclonal antisera, there were antigenic differences between viruses from these genotypes and the BPI3Va viruses that are included in currently marketed bovine vaccines. These findings suggest that inclusion of viruses isolated more recently could improve the protection provided by vaccines. Similarly it was found that a new subtype of BoCV has come to predominate in the field. While the above research focused on variation over time in known viral species, other projects focused on newly emerging viruses. It was found that the emerging pestivirus species and HoBi-like viruses, can establish persistent lifelong infections in cattle. Current diagnostics, designed to detect BVDV persistently infected (PI), were not reliable for the detection of HoBi-live virus PI cattle. Because cattle persistently infected with HoBi-like viruses could act as very efficient vectors for introduction of this emerging virus into na�ve herds, it is important that better tests are developed so that PI animals can be removed from the population. For this reason HoBi-like virus specific tests were designed and tested. In addition, research was also conducted on two other emerging pestiviruses species, Bungowannah virus (which causes reproductive losses in pigs) or Pronghorn virus (which circulates in North American wildlife). While neither of these emerging viruses appear to be bovine pathogens, comparison of sequence and antigenic data to known species allows the determination of conserved and variable characteristics that may be associated with host selection or virulence. Information garnered from these studies can be used in improving detection and control. Finally, different vector systems were evaluated for the expression of viral proteins derived from HoBi-like viruses. Viral protein was successfully expressed and will be used in the generation of reagents to be used in diagnostic tests. Supporting Objective 2, research for FY15 focused on generating animal models that replicated BRDC under controlled conditions and elucidating the effects of viral infection on immune function. BRDC is difficult to replicate in the research setting because a complex interaction of multiple factors contribute to the clinical presentation. One research initiative looked at dual infections with bacterial and viral pathogens. In a series of studies dual BRSV and Pasteurella multocida (P. multocida) infections were evaluated as a BRDC model. The calves which received both BRSV and P. multocida had generally more severe lung lesions than the calves infected with BRSV or P. multocida only. Similarly another research initiative examined dual infections with two viruses. BVDV and BoCV are frequently isolated from cattle suffering from BRDC. However, animal models based on infection with either of these viruses alone have had limited success in reproducing respiratory disease. Further, is has been reported that simultaneous exposure of cattle to BVDV and BoCV did not result in BRDC. In this study seven infection protocols were compared. The only infection protocols that resulted in lung lesions consistent with respiratory disease were BVDV followed 6 or 9 days later by BoCV. These results indicate that while single infection with BVDV or BoCV do not result in respiratory disease, sequential infections of BVDV followed by BoCV can result in gross and microscopic lesions that are consistent with respiratory disease. The window of time in which BoCV infection is most likely to result in respiratory disease coincides with the peak of immunosuppression caused by BVDV. These studies of dual bacterial/viral infections and dual viral infections are important because animal models of BRDC are needed to test the efficacy of control measures such as vaccination. It has been proposed that one of the factors contributing to BRDC is immune suppression, associated with viral infections, that predisposes cattle to more severe secondary infections. Viral associated immunosuppression was examined by evaluating cytokine levels following infection and by making libraries of the transcripts generated in immune cells following in vivo viral infections. Previous in vitro studies have shown that BVDV infections impair white blood cell function. ARS Researchers in Ames, IA conducted studies that examined the effects of in vivo BVDV infection on monocyte and macrophage function using strains of differing virulence. Monocytes and macrophages play a critical role in non- specific defense (innate immunity), and also help initiate specific defense mechanisms (adaptive immunity). Cytokine production by monocytes and macrophages were evaluated at early or late time points following infection with BVDV 2 strains of high (HV) or low virulence (LV). The results of these studies suggest that BVDV may have evolved strategies that impair the generation and differentiation of cells involved in the immune response. These findings contribute the understanding of the immune suppression that occurs following BVDV infections and could lead to the development of means decrease or eliminate this immune suppression. Supporting Objective 3, research focused on evaluating changes in serum vitamin D and E levels associated with clinical disease or seasonal variation. Vitamin D and E levels are of interest because serum levels of these vitamins have been associated with improved immune response to vaccination or infection. While previous studies in young animals have shown an association between vitamin deficiencies and increased risk of infectious disease there is little information available regarding serum vitamin D and E levels during infection. To characterize the effects of acute infection on vitamin D and E status of the neonate, neonatal calves were experimentally infected with high virulence BVDV. The development of severe clinical signs corresponded to decreases in vitamin D and vitamin E levels in serum. Further studies are needed to determine if supplementing neonatal rations with extra vitamin D or E during viral infections would diminish disease severity and duration. Vitamin D levels in serum may result from ingestion of vitamin D supplements or it can be produced in the skin by exposure to ultraviolet B containing sunlight. Because producers recognize the importance of vitamin D to immune function, most commercial feeds are supplemented with vitamin D. A study was conducted that measured seasonal variation in concentration of circulating vitamin D in beef cattle reared in the Central United States and fed commonly used dietary vitamin D supplements. Measurements were taken at four different time periods, 2 to 3 months after birth (spring), late summer, early fall and midwinter, during 2 consecutive years. It was found that while vitamin D supplemented rations were fed during all four periods, vitamin D serum levels were below recommended levels in spring and winter when exposure to sunlight was the lowest. These results suggest that dietary vitamin D requirements may need to be adjusted by season. Accomplishments 01 Rapid sequencing of viral genomes. Generation and comparison of full length sequences of viral genomes is important to the study of viral evolution and identification of new viruses. The difficulty, time and expense of generating full-length sequences hampers these studies. Previously, ARS researchers in Ames, IA developed a method for rapidly sequencing complete viral genomes. This technology was used to compare field strains of viruses isolated from cattle in different years, to generate the first sequence of an emerging pestivirus and to identify a heretofore unknown type of adenovirus. Multiple benefits from these studies included the means to do a better job of matching vaccines strains to virus strains circulating in the field and the improved detection and characterization of new and/or emerging viruses. 02 Transmission of an emerging virus from cattle to other domestic species. Before programs can be designed to control emerging viruses, it is necessary to determine which species can be infected. HoBi-like viruses are an emerging species of pestiviruses associated with enteric, respiratory and reproductive disease in cattle and water buffalo. While cattle appear to be the principal host of this emerging virus, little is known about the potential for these viruses to be transmitted to other domestic species. In a series of studies, ARS researchers in Ames, IA demonstrated that cattle infected with HoBi-like viruses can transmit the virus not just to only other cattle but to, sheep, goats and pigs. These studies demonstrate that HoBi-like viruses have the potential to infect multiple animal production industries. This information demonstrates that the evaluation of the potential economic impact for the US resulting from the introduction of this emerging virus must factor in not just potential losses to the cattle industry but also potential losses to the swine and small ruminant industries.
Impacts
(N/A)
Publications
- Casas, E., Hessman, B.E., Keele, J.W., Ridpath, J.F. 2015. A genome-wide association study for the incidence of persistent bovine viral diarrhea virus infection in cattle. Animal Genetics. 46:8-15. DOI: 10.1111/age. 12239.
- Fulton, R.W., Herd, H.R., Sorensen, N.J., Confer, A.W., Ritchey, J.W., Ridpath, J.F., Burge, L.J. 2014. Enteric disease in postweaned beef calves associated with a Bovine coronavirus clade 2. Journal of Veterinary Diagnostic Investigation. 27(1)97-101. DOI: 1177/1040638714559026.
- Bauermann, F.V., Ridpath, J.F. 2015. HoBi-like viruses � the typical 'atypical bovine pestivirus'. Animal Health Research Reviews. 16(1):64-69. DOI: 10.1017/S146625231500002X.
- Bauermann, F.V., Falkenberg, S.M., Vander Ley, B.D., Decaro, N., Brodersen, B.W., Harmon, A., Hessman, B., Flores, E.F., Ridpath, J.F. 2014. Generation of calves persistently infected with HoBi-like pestivirus and comparison of methods for detection of these persistent infections. Journal of Clinical Microbiology. 52(11):3845-3852. DOI: 10.1128/JCM.01563- 14.
- Casas, E., Lippolis, J.D., Kuehn, L.A., Reinhardt, T.A. 2015. Seasonal variation in vitamin D status of beef cattle reared in the central United States. Domestic Animal Endocrinology. 52:71-74. DOI: 10.1016/j.domaniend. 2015.03.003.
- Neill, J.D., Ridpath, J.F., Valayudhan, B.T. 2015. Identification and genome characterization of genotype B and genotype C bovine parainfluenza type 3 viruses isolated in the United States. BioMed Central (BMC) Veterinary Research. 11:112. DOI: 10.1186/s12917-015-0431-8.
- Darweesh, M.F., Rajput, M.K., Braun, L.J., Ridpath, J.F., Neill, J.D., Chase, C.C. 2015. Characterization of the cytopathic BVDV strains isolated from 13 mucosal disease cases arising in a cattle herd. Virus Research. 195:141-147. DOI: 10.1016/j.viruses.2014.09.015.
- Neill, J.D. 2014. Complete genome sequence of the San Miguel sea lion virus-8 reveals that it is not a member of the vesicular exanthema of swine virus/San Miguel Sea Lion virus species of the Caliciviridae. Genome Announcements. 2(6). e01286-14. DOI: 10.1128/genomeA.01286-14.
- Neill, J.D., Dubovi, E.J., Ridpath, J.F. 2015. Identification of amino acid changes in the envelope glycoproteins of bovine viral diarrhea viruses isolated from alpaca that may be involved in host adaptation. Veterinary Microbiology.
- Ridpath, J.F. 2015. Emerging pestiviruses infecting domestic and wildlife hosts. Animal Health Research Reviews. 16(1):55-59. DOI: 10.1017/ S1466252315000067.
- Kirkland, P.D., Frost, M.J., King, K.R., Finlaison, D.S., Hornitzky, C.L., Gu, X., Richter, M., Reimann, L., Dauber, M., Schirrmeier, H., Beer, M., Ridpath, J.F. 2015. Genetic and antigenic characterization of Bungowannah virus, a novel pestivirus. Veterinary Microbiology. 178(3-4):252-259. DOI: 10.1016/j.vetmic.2015.05.014.
- Kane, S.E., Holler, L., Braun, L.J., Neill, J.D., Young, D.B., Ridpath, J. F., Chase, C.C. 2015. Bovine viral diarrhea virus outbreak in a beef cow herd in South Dakota. Journal of the American Veterinary Medical Association. 246(12):1358-1362. DOI 10.2460/javma.246.12.1358.
- Ridpath, J.F. 2013. Immunology of BVDV vaccines. Biologicals. 41(1):14-19.
- Loy, J.D., Gander, J., Mogler, M., Vander Veen, R., Ridpath, J.F., Harris, D.L., Kamrud, K. 2013. Development and evaluation of a replicon particle vaccine expressing the E2 glycoprotein of bovine viral diarrhea virus (BVDV) in cattle. Virology Journal. 10:35. doi: 10.1186/1743-422x-10-35.
- Fulton, R.W., Rezabek, G.B., Grant, R., Ridpath, J.F., Burge, L.J. 2014. Diverse outcomes of bovine viral diarrhea virus infections in a herd naturally infected during pregnancy - a case study. Bovine Practitioner. 48(2):95-98.
- Casas, E., Duan, Q., Schneider, M.J., Shackelford, S.D., Wheeler, T.L., Cundiff, L.V., Reecy, J.M. 2014. Polymorphisms in the calpastatin and mu- calpain genes associated with beef iron content. Animal Genetics. 45(2) :283-284. DOI: 10.1111/age.12108.
- Hansen, T.R., Smirnova, N.P., Webb, B.T., Bielefeldt-Ohmann, H., Sacco, R. E., Van Campen, H. 2015. Innate and adaptive immune responses to in utero infection with bovine viral diarrhea virus. Animal Health Research Reviews. 16(1):15-26. DOI: 10.1017/S1466252315000122.
- Andersson, L., Archibald, A.L., Bottema, C.D., Brauning, R., Burgess, S.C., Burt, D.W., Casas, E., Cheng, H.H., Clarke, L., Couldrey, C., Dalrymple, B.P., Elski, C.G., Foissac, S., Giuffra, E., Groenen, M.A., Hayes, B.J., Huang, L.S., Khatib, H., Kijas, J.W., Kim, H., Lunney, J.K., McCarthy, F.M. , McEwan, J.C., Moore, S., Nanduri, B., Notredame, C., Palti, Y., Plastow, G.S., Reecy, J.M., Rohrer, G.A., Sarrapoulou, E., Schmidt, C.J., Silverstein, J., Tellam, R.L., Tixier-Biochard, M., Tosser-Klopp, G., Tuggle, C.K., Vilkki, J., White, S.N., Zhao, S., Zhou, H. 2015. Coordinated international action to accelerate genome-to-phenome with FAANG, The Functional Annotation of Animal Genomes project. Genome Biology. 16:57. DOI:10.1186/S13059-015-0622-4.
- Falkenberg, S.M., Ridpath, J.F., Vander Ley, B., Bauermann, F.V., Carroll, J.A. 2014. Comparison of temperature fluctuations at multiple anatomical locations in cattle during exposure to bovine viral diarrhea virus. Livestock Science. 164(2014):159-167. DOI:10.1016/j.livsci.2014.03.018.
- Falkenberg, S.M., Ridpath, J.F., Tait Jr, R.G., Vander Ley, B., Bauermann, F.V., Reecy, J.M. 2015. Association of serum antibody levels following vaccination with a modified live BVDV vaccine and protection from clinical disease upon challenge. Jacobs Journal of Vaccines and Vaccination. 1(1) :002.
- Schaut, R.G., McGill, J.L., Neill, J.D., Ridpath, J.F., Sacco, R.E. 2015. Bovine viral diarrhea virus type 2 in vivo infection modulates TLR4 responsiveness in differentiated Myeloid cells which is associated with decreased MyD88 expression. Virus Research. 208:44-55. DOI: 10.1016/j. viruses.2015.05.017.
- Tait, R.G., Jr., Shackelford, S.D., Wheeler, T.L., King, D.A., Keele, J.W., Casas, E., Smith, T.P., Bennett, G.L. 2014. CAPN1, CAST, and DGAT1 genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in a beef cattle population selected for haplotype and allele equalization. Journal of Animal Science. 92(12):5382- 5393.
- Richeson, J.T., Pinedo, P.J., Kegley, E.B., Powell, J.G., Gadberry, M.S., Beck, P.A., Falkenberg, S.M. 2013. Association of hematological variables and castration status at the time of arrival at a research facility with the risk of bovine respiratory disease in beef calves. Journal of the American Veterinary Medical Association. 243(7):1035-1041. DOI: 10.2460/ javma.243.7.1035.
- Nonnecke, B.J., McGill, J.L., Ridpath, J.F., Sacco, R.E., Lippolis, J.D., Reinhardt, T.A. 2014. Acute phase response elicited by experimental bovine diarrhea virus (BVDV) infection is associated with decreased vitamin D and E status of vitamin-replete preruminant calves. Journal of Dairy Science. 97(9):5566-5579. DOI: 10.3168/jds.2014-8293.
- Ridpath, J.F., Neill, J.D. 2015. Pestiviruses: old enemies and new challenges. Animal Health Research Reviews. 16(1):1-3. DOI: 10.1017/ S1466252315000134.
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Progress 10/01/13 to 09/30/14
Outputs
Progress Report Objectives (from AD-416): Objective 1: Determine the impact of variant and emerging viruses on the development and control of respiratory disease in ruminants. Develop means to detect and survey for variant viruses and develop models for evaluating infections with emerging variant viruses. Subobjectives: (1a) Determine impact of variant and emerging viruses; (1b) Improve current surveillance methods and diagnostic tools used to detect and control emerging viruses. Objective 2: Elucidate the host-pathogen interactions associated with the Bovine Respiratory Disease Complex (BRDC) by defining host pathways modulated as a result of viral infections and characterizing the role of stress and immunological related host effector molecules in BRDC. Subobjectives: (2a) Define interactions of viral pathogens that may contribute to the development of respiratory disease; (2b) Define modulation of host immune response to viral infection associated with stress caused by vitamin D insufficiency. Objective 3: Evaluate formulations and delivery systems for vaccination of neonates by identifying means to modulate stress and immunological factors associated with BRDC. Generate identification criteria and means to generate �vaccine ready� calves to develop intervention strategies for controlling viral respiratory infections of ruminants. Subobjectives: (3a) Identify factors, associated with common management practices, that modulate immune function in neonatal calves; (3b) Evaluate candidate vaccine for use in calves. Approach (from AD-416): The goal of this project is to reduce the incidence and impact of viral infections in ruminants with particular emphasis on viral infections that contribute to respiratory disease in cattle. The project encompasses three distinct but interrelated research efforts. The first is to determine the incidence and impact of variant viruses, such as subgenotypes of bovine viral diarrhea virus (BVDV), and emerging viruses, such as HoBi-like viruses, to bovine respiratory disease. The purpose of this research is to determine if new antigens, representing variant and emerging viruses, need to be included in vaccines. The second is to examine the interaction of host and virus in respiratory disease. Included in this effort will be the study of host immune dysfunction, resulting from viral infection, nutrition, or stress. The purpose of this research is to define factors that contribute to respiratory disease in order to develop means of intervention that negate or ameliorate those factors. The third is to determine means by which host resistance to viral infection can be enhanced with emphasis on improving protective innate and acquired immune responses in calves. The information generated from these three research areas will be used in the development of intervention strategies to control and eliminate viral pathogens. Improved control of viral pathogens will benefit consumers by ensuring a healthful food supply, enhance animal health and well-being, and reduce production costs for farmers and ranchers. Substantial progress was made on each of the three objectives of this research project. The goal of this project is to reduce viral infection in ruminants that contribute respiratory disease in cattle. Known viruses associated with bovine respiratory disease complex (BRDC) include bovine viral diarrhea viruses (BVDV), infectious bovine rhinotracheitis virus (IBR), bovine respiratory disease virus (BRSV), bovine parainfluenza virus 3 (BPI3V) and bovine coronavirus (BoCV). Recently a pestivirus variously referred to as HoBi-like virus, atypical bovine pestivirus or BVDV3 has been recognized as a bovine respiratory pathogen infecting cattle in South America, Asia, Southeast Asia and Europe. Supporting Objective 1, research for FY 14, focused on two fronts; detecting changes in bovine respiratory viruses circulating in US cattle populations, over the last three to five decades, and evaluating the risk that the introduction of HoBi-like viruses pose to the US agriculture. Surveys of BoCV and BPI3V strains were completed this year. Surveys of BRSV and IBR have been initiated. In previous years a survey of BVDV strains was completed. It appears that in all viral species examined, significant genomic drift has occurred over time. Studies determining whether the genomic changes observed affect efficacy of diagnostics as vaccines are nearly finished (BVDV and BoCV), in progress (BRSV and BPI3V) or in the planning stage (IBR). It was demonstrated that calves persistently infected with HoBi-like viruses could transmit the virus to other cattle, sheep, goats and pigs. It was also shown that commercially available tests, designed to detect BVDV infection or BVDV exposure, could not be used to detect and differentiate outbreaks from BVDV outbreaks. Bench validation of tests to be used in surveys to determine incidence of exposure of cattle in the US and South America to HoBi-like viruses were completed. Design strategies were developed for these surveys with the input of collaborators in the U.S., Brazil and Argentina. Different types of samples, used to detect persistent infections with either BVDV or HoBi-like virus or acute infections of BoCV, were compared and polyclonal sera that can be used to differentiate between BVDV and HoBi-like viruses were generated. Supporting Objective 2, research for FY14 focused on identifying viral factors and host responses that are associated with either limiting or conversely increasing viral pathogenesis. A series of studies evaluating single and dual infections of BVDV and BoCV were completed. It was found that the immune suppression following infection of neonatal calves, particularly as measured by a decrease in thymus tissue, was significant in single infections of BVDV and dual infections of BVDV and BoCV. This observation may have practical impact as loss of thymus tissue as a neonate may prevent the normal maturation of the bovine immune system. Signs of respiratory disease were only seen in calves first infected by BVDV followed 6 to 8 days later by BoCV, suggesting that BVDV immune suppression increases the pathogenesis associated with BoCV. These observations are key to developing an experimental model for BRDC. A challenge model was designed and tested that allowed the measurement of vitamin D effects on the outcome of BRSV infections. Analysis of vitamin D levels during infection with high and low virulent BVDV infections demonstrated that severe clinical signs were associated with significant drops in vitamin D levels in serum. Studies examining the differences in gene transcripts in circulating immune cells isolated from non-infected cattle, cattle infected with either BVDV or BoCV alone or cattle dual infected with both BVDV and BoCV were initiated. These studies will shed light on those immune cell functions that are important in the development of respiratory disease. In collaboration with Auburn University, studies comparing the virulence of BPI3V field strains were initiated. The studies are on track to be completed next fiscal year. Supporting Objective 3, research for FY14, focused on evaluating immune response to vaccination and developing a novel vaccine platform. In collaboration with the Department of Animal Science Texas A&M University a study to assess traditional feedlot performance traits in cattle of known genetic background following standardized vaccination protocol and subsequent BVDV challenge was completed. The virus used in these studies was a low virulence field strain. Both vaccinated and nonvaccinated cattle presented with mild fever and reduced rate of gain following exposure to the low virulence BVDV field strain. However, typical feedlot management, which relies on visual assessment to detect unhealthy animals would have missed the infection in these animals. On average, fever was lower and of shorter duration and the effect on production values was less in the vaccinated group. This study revealed that while vaccination reduces the effects of infection it does not eliminate them and that subclinical infections can have significant impact on production values. In another study conducted in collaboration with the Animal Science Department of Iowa State University, calves were vaccinated at the time of weaning and followed through calf hood development, feedlot phase and harvesting. The response to vaccination was determined by measuring antibodies in serum that were generated in response to vaccination. A higher level of antibodies reflects a more robust response to vaccination. Growth rates and meat quality factors were evaluated. It was found that there was no difference in growth rates and meat quality between animals that had a high level of antibodies following vaccination and animals that had a low level of antibodies. Thus a robust response to vaccination did not affect growth or meat quality indicating that producers should not be concerned that calf hood vaccinations have a negative effect on production. As part of our effort to develop better models to evaluate vaccines, we compared field isolates to the reference strain of BRSV currently used in vaccine testing. The field isolates caused more severe clinical signs compared to the reference strain. Using a strain of virus that is lower in virulence than currently circulating strains in testing vaccines could result in tested efficacy rates that are artificially high. This research indicates that current reference strains need to be replaced with higher virulence field strains. The in vitro evaluation of a nanoparticle vaccine containing a portion of a BRSV structural protein, known as the G protein, was completed. This testing indicated that the vaccines would work better if the entire G protein was included. Work is currently underway to express the G protein in the baculovirus system. Accomplishments 01 Development and implementation of method to rapidly sequence the genomes of multiple RNA viruses simultaneously. ARS researchers in Ames, IA have been using collections of viruses archived by diagnostic laboratories over the last 50 years to examine changes in viral populations over time that result in reduced effectiveness of vaccines. The difficulty, time requirement and expense of generating full-length sequences individually from each archived sample hampered these studies. ARS researchers developed a protocol, based on next generation sequencing, which allowed the rapid and simultaneous full genome sequencing of multiple archived viruses. This protocol was used to generate full or nearly full length genomic sequences from over four hundred archived viruses including bovine viral diarrhea viruses (BVDV), bovine coronaviruses (BoCV), bovine respiratory syncytial viruses (BRSV) and bovine parainfluenza 3 (BPIV3) viruses. Comparison of these sequences to reference and vaccine strains revealed that the populations of these viruses that are currently circulating in the United States are significantly different from the viruses used in vaccines. Further analysis, based on the ability of serum from vaccinated animals to neutralize viruses, conducted with the BVDV and BoCV isolates demonstrated these differences can lead to vaccine failure. Studies duplicating these comparisons with BRSV and BPI3V are planned. Matching vaccine strains to currently circulating strains should increase the effectiveness of vaccines, thus providing producers with improved tools to fight bovine respiratory disease (BRD). 02 Characterization of HoBi-like virus infections and development of tools to assist in its control. Pestiviruses are a genus of virus that cause several economically important diseases in commercial livestock. The pestivirus associated disease that causes the greatest problem for dairy and beef producers is known as bovine viral diarrhea (BVD). The name is misleading as BVD encompasses a number of different clinical presentations besides enteric disease including respiratory disease, reproductive disease and immune suppression. Previous research conducted by ARS researchers in Ames, IA demonstrated two different species of virus, bovine viral diarrhea virus 1 (BVDV1) and bovine viral diarrhea virus 2 (BVDV2) that caused BVD. Recently a third species of virus, referred to as HoBi-like virus, has been found that causes BVD. ARS researchers in Ames, IA revealed that clinical signs associated with HoBi-like infection are indistinguishable from those observed in BVDV1 and BVDV2 infections. Calves persistently infected with HoBi like virus were generated. These persistently infected (PI) calves, which appeared normal, shed large amounts of viruses continually and were able to transmit the virus to other cattle, sheep, goats and pigs. Samples from these PI calves were used to compare commercially available and experimental prototypes tests, to determine how effective they were in detecting HoBi-like virus infection. While some commercially available tests designed to detect BVDV infections did detect HoBi-like virus in some samples, these tests could not be used to differentiate a BVDV infection from a HoBi-like infection. Thus, these commercial tests cannot be used in a surveillance program to prevent the introduction of HoBi-like viruses into the United States. The information gathered in these studies will be used to support the development of guidelines to avoid introduction and/or dissemination of this emerging viral in the United States. 03 Completion of genome-wide association study for incidence of genomic regions associated with persistent bovine viral diarrhea virus (BVDV) in feedlot cattle. The availability of the bovine genome has allowed the identification of thousands of changes in the sequence known as single nucleotide polymorphisms. These single nucleotide polymorphisms have supported the development of high-density genotyping arrays and an increase in the ability to identify genomic variation associated with complex traits such as infectious diseases in cattle. BVDV plays an important economical role in livestock production. BVDV fetal infections can result in lifelong persistent infections. Persistently infected (PI) cattle may appear unthrifty with congenital defects or may appear clinically normal. While many PI calves die in the first 3 months of life, a significant number live long enough to enter the feedlot system. A study was conducted by ARS researchers in Ames,IA to determine if genomic regions harboring single nucleotide polymorphisms could be associated with presence or absence of persistent BVDV infection in feedlot cattle. Using a large population (n= 2,400 animals) it was possible to identify DNA differences associated with persistent BVDV in cattle in feedlots. These DNA differences reside within or in the vicinity of genes involved in several biological processes, including immune responses, which may contribute to the animal's ability to survive the persistent infection. DNA differences identified in the present study will be used, along with further studies, to understand why some cattle die as neonates and why some appear healthy and are sold into feedlots.
Impacts
(N/A)
Publications
- Weber, M.N., Mosena, A.C., Simoes, V.D., Almeida, L.L., Pessoa, C.R., Budaszewski, R.F., Silva, T.R., Ridpath, J.F., Riet-Correa, F., Driemeier, D., Canal, C.W. 2014. Clinical presentation resembling mucosal disease associated with 'HoBi'-like Pestivirus in a field outbreak. Transboundary and Emerging Diseases. DOI: 10.1111/TBED.12223.
- Ridpath, J.F. 2013. A need to define characteristics to be used in the taxonomy of the expanding pestivirus genus. Berliner Muchener Tierarztliche Wochenschrift. 126(11-12):462-467.
- Ridpath, J.F., Neill, J.D., Chiang, Y., Waldbillig, J. 2014. Stability of Bovine viral diarrhea virus 1 nucleic acid in fetal bovine samples stored under different conditions. Journal of Veterinary Diagnostic Investigation. 26(1):6-9.
- Pecora, A., Malacari, D.A., Ridpath, J.F., Perezaguirreburualde, M.S., Combessies, G., Odeon, A., Romera, A.S., Golemba, M., Wigdorovitz, A. 2014. First finding of genetic and antigenic diversity in 1b-BVDV isolates from Argentina. Research in Veterinary Science. 96(1):204-212.
- Decaro, N., Mari, V., Lucente, M.S., Sciarretta, R., Elia, G., Ridpath, J. F., Buonavoglia, C. 2013. Detection of a Hobi-like virus in archival samples suggests circulation of this emerging pestivirus species in Europe prior to 2007. Veterinary Microbiology. 167(3-4):307-313.
- Tait Jr., R.G., Downey, E.D., Mayes, M.S., Park, C.A., Ridpath, J.F., Garrick, D.J., Reecy, J.M. 2013. Evaluation of response to bovine viral diarrhea virus type 2 vaccination and timing of weaning on yearling ultrasound body composition, performance, and carcass quality traits in Angus calves. Journal of Animal Science Supplement. 91:5466-5476.
- Downey, E.D., Mayes, M.S., Tait, Jr., R.G., Ridpath, J.F., Garrick, D.J., Reecy, J.M. 2013. An evaluation of circulating bovine diarrhea virus type 2 maternal antibody level and response to vaccination in Angus calves. Journal of Animal Science. 91:4440-4450.
- Newcomer, B.W., Neill, J.D., Marley, M.S., Ridpath, J.F., Givens, M.D. 2013. Mutations induced in the NS5B gene of bovine viral diarrhea virus by antiviral treatment convey resistance to the compound. Virus Research. 174(2013):95-100.
- Ridpath, J.F., Falkenberg, S.M., Bauermann, F.V., Vander Ley, B.L., Do, Y., Flores, E.F., Rodman, D.M., Neill, J.D. 2013. Comparison of clinical presentation following acute infections of cattle with either a high virulence or low virulence BVDV to clinical presentation following infection with a HoBi-like pestivirus. American Journal of Veterinary Research. 74:438-442.
- Falkenberg, S.M., Johnson, C., Bauermann, F.V., McGill, J.L., Palmer, M.V., Ridpath, J.F., Sacco, R.E. 2014. Changes observed in the thymus and lymph nodes 14 days after exposure to BVDV field strains of enhanced or typical virulence in neonatal calves. Veterinary Immunology and Immunopathology. 160(1-2):70-80.
- Neill, J.D., Ridpath, J.F. 2014. Complete genome sequence of a cytopathic/ noncytopathic pair of border disease viruses. Genome Announcements. 2(2). DOI: 10.1128/genomeA.00260-14.
- Neill, J.D., Bayles, D.O., Ridpath, J.F. 2014. Simultaneous rapid sequencing of multiple RNA virus genomes. Journal of Virological Methods. 201:68-72. DOI: 10.1016/j.viromet.2014.02.016.
- Bauermann, F.V., Flores, E.F., Falkenberg, S.M., Ridpath, J.F. 2014. Lack of evidence for the presence of emerging HoBi-like viruses in fetal bovine serum lots originated in North America and packaged in the United States of America. Journal of Veterinary Diagnostic Investigation. 26(1):10-17. DOI: 10.1177/1040638713518208.
- Tait Jr, R.G., Shackelford, S.D., Wheeler, T.L., King, D.A., Casas, E., Thallman, R.M., Smith, T.P., Bennett, G.L. 2014. �-Calpain, calpastatin, and growth hormone receptor genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in Angus cattle selected to increase minor haplotype and allele frequencies. Journal of Animal Science. 92(2):456-466.
- Passler, T., Riddell, K.P., Edmondson, M.A., Chamorro, M.F., Neill, J.D., Broderson, B.W., Walz, H.L., Galik, P.K., Zhang, Y., Walz, P.H. 2014. Experimental infection of pregnant goats with bovine viral diarrhea virus (BVDV)1 or 2. Veterinary Research. 45:38. DOI: 10.1186/1297-9716-45-38.
- Sacco, R.E., McGill, J.L., Pillatzki, A.E., Palmer, M.V., Ackermann, M.R. 2014. Respiratory syncytial virus infection in cattle. Veterinary Pathology. 51(2):427-436. DOI: 10.1177/0300985813501341.
- Derscheid, R.J., van Geelen, A., McGill, J.L., Gallup, J.M., Cihlar, T., Sacco, R.E., Ackermann, M.R. 2013. Human respiratory syncytial virus Memphis 37 grown in HEp-2 cells causes more severe disease in lambs than virus grown in vero cells. Viruses. 5(11):2881-2897. DOI: 10.3390/v5112881.
- Eberle, K., Waters, T.E., Jensen, E.D., Venn-Watson, S., Sacco, R.E. 2013. Development and application of specific cytokine assays in tissue samples from a bottlenose dolphin with hyperinsulinemia. Frontiers in Endocrinology. 4:134. DOI: 10.3389/fendo.2013.00134.
- Smirnova, N.P., Webb, B.T., McGill, J.L., Schaut, R.G., Bielefeldt-Ohmann, H., Van Campen, H., Sacco, R.E., Hansen, T.R. 2014. Induction of interferon-gamma and downstream pathways during establishment of fetal persistent infection with bovine viral diarrhea virus. Virus Research. 183:95-106. DOI: 10.1016/j.virusres.2014.02.002.
- Neill, J.D., Ridpath, J.F., Fisher, N., Grundhoff, A., Postel, A., Becher, P. 2014. Complete genome sequence of Pronghorn Virus, a Pestivirus. Genome Announcements. 2(3):e00575-14. DOI: 10.1128/genomeA.00575-14.
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Progress 10/01/12 to 09/30/13
Outputs
Progress Report Objectives (from AD-416): Objective 1: Determine the impact of variant and emerging viruses on the development and control of respiratory disease in ruminants. Develop means to detect and survey for variant viruses and develop models for evaluating infections with emerging variant viruses. Subobjectives: (1a) Determine impact of variant and emerging viruses; (1b) Improve current surveillance methods and diagnostic tools used to detect and control emerging viruses. Objective 2: Elucidate the host-pathogen interactions associated with the Bovine Respiratory Disease Complex (BRDC) by defining host pathways modulated as a result of viral infections and characterizing the role of stress and immunological related host effector molecules in BRDC. Subobjectives: (2a) Define interactions of viral pathogens that may contribute to the development of respiratory disease; (2b) Define modulation of host immune response to viral infection associated with stress caused by vitamin D insufficiency. Objective 3: Evaluate formulations and delivery systems for vaccination of neonates by identifying means to modulate stress and immunological factors associated with BRDC. Generate identification criteria and means to generate �vaccine ready� calves to develop intervention strategies for controlling viral respiratory infections of ruminants. Subobjectives: (3a) Identify factors, associated with common management practices, that modulate immune function in neonatal calves; (3b) Evaluate candidate vaccine for use in calves. Approach (from AD-416): The goal of this project is to reduce the incidence and impact of viral infections in ruminants with particular emphasis on viral infections that contribute to respiratory disease in cattle. The project encompasses three distinct but interrelated research efforts. The first is to determine the incidence and impact of variant viruses, such as subgenotypes of bovine viral diarrhea virus (BVDV), and emerging viruses, such as HoBi-like viruses, to bovine respiratory disease. The purpose of this research is to determine if new antigens, representing variant and emerging viruses, need to be included in vaccines. The second is to examine the interaction of host and virus in respiratory disease. Included in this effort will be the study of host immune dysfunction, resulting from viral infection, nutrition, or stress. The purpose of this research is to define factors that contribute to respiratory disease in order to develop means of intervention that negate or ameliorate those factors. The third is to determine means by which host resistance to viral infection can be enhanced with emphasis on improving protective innate and acquired immune responses in calves. The information generated from these three research areas will be used in the development of intervention strategies to control and eliminate viral pathogens. Improved control of viral pathogens will benefit consumers by ensuring a healthful food supply, enhance animal health and well-being, and reduce production costs for farmers and ranchers. Viruses associated with bovine respiratory disease complex (BRDC) include bovine viral diarrhea viruses (BVDV), infectious bovine rhinotracheitis virus (IBR), Parainfluenza 3 virus (PI3), Bovine respiratory syncytial virus (BRSV) and bovine corona virus (BoCV). In support of objective 1, ARS researchers at Ames, IA are in the process of comparing currently circulating BVDV, IBR, PI3, BRSV and BoCV to viral strains currently in vaccines. Based on comparison of viral genetic material, the currently circulating viruses differ from vaccine viruses suggesting that protection against BRDC may be improved by using new vaccine strains. HoBi-like viruses are an emerging species of pestivirus, related to BVDV. NADC researchers demonstrated that HoBi-like viruses cause persistent infections in cattle. These persistently infected cattle can transmit the virus to other cattle, sheep, pigs and goats. Exposure to HoBi-like viruses could be differentiated from infection or vaccination with BVDV using a test designed by ARS NADC researchers. This test was used to screen serum samples originating in the U.S. No exposure to HoBi-like viruses was detected. In support of objective 2, ARS researchers in Ames, IA compared immune tissue collected from non infected calves and calves infected with BVDV strains of varying virulence. They found that regardless of virulence, BVDV infections leave calves with damaged lymphoid tissues which might make them less able to fight off subsequent infections. We have also examined host genetic markers that are associated with BVDV immunosuppression and persistent infection. Studies are being designed to determine the function of these genetic markers. We have evaluated the effects of vitamin D status on immune response to infection with BRSV and BVDV. Results suggested that vitamin D status has a positive effect the immune response to BRSV and BVDV infections. We also found that proteins produced by BVDV bind host proteins associated with immune response. This may slow the host�s ability to fight off pathogens. In support of Objective 3, two collaborations focused on vaccine development. In one, ARS researchers in Ames, IA made a vaccine against BRSV based on the attachment of proteins to small spheres (nanoparticles). This vaccine has been tested in cultured cells and plans are to test it in cattle. In another, ARS researchers at Ames, IA and a commercial biologics company developed a killed BVDV vaccine, based on expression of BVDV proteins in a defective Alphavirus particle called a replicon. Replicons infect cells and make viral proteins but do not to give rise to offspring viruses that are able to infect cells. It was shown that the new vaccine protected calves from disease. A third collaboration between ARS researchers in Ames, IA and a land grant university examined response to vaccination in cattle herds. It was found that not all cattle are protected from infection following vaccination. Future research will focus on why some cattle are protected and others are not. Accomplishments 01 Evaluation of protection afforded, by current vaccines, against a newly emerging virus related to bovine viral diarrhea viruses (BVDV). Recently a new group of viruses, known as HoBi like viruses, have been isolated from cattle in Brazil, Italy and Thailand. HoBi like viruses are related to bovine viral diarrhea viruses (BVDV) and cause very similar diseases in cattle. Introduction of HoBi like viruses into North America could result in significant economic loss by cattle producers. There are no vaccines available for the prevention of infection of cattle by HoBi like viruses. ARS researchers at Ames, Iowa performed studies to determine if cattle vaccinated using BVDV vaccines would be protected against infection with HoBi like viruses. It was found that cattle vaccinated against BVDV would have little or no protection against infection with HoBi like viruses. This suggests that new vaccines, specific for HoBi like viruses, need to be developed to control this emerging pathogen. 02 Evaluation of changes in respiratory viruses over time that might impact effectiveness of vaccines. Bovine respiratory disease complex (BRDC) appears to be the result of interactions of a number of factors including stress, infection with bacterial pathogens and infection with viral pathogens. Viruses associated with BRDC include BVDV, infectious bovine rhinotracheitis virus (IBR), Parainfluenza 3 virus (PI3), Bovine respiratory syncytial virus (BRSV) and bovine corona virus (BoCV). ARS researchers at Ames, Iowa have entered into a series of studies to examine if evolution of viruses over time is reducing the effectiveness of vaccines. In an initial study, researchers at the National Animal Disease Center (NADC) collaborated with a land grant university to examine changes in bovine corona viruses (BoCV), which have recently been isolated from cattle with BRDC. BoCV were first discovered over 50 years ago in samples from calves suffering from diarrhea. In the initial study the BoCV from recent respiratory cases were compared with the BoCV from diarrhea cases (enteric disease). It was found that the respiratory viruses were different from the enteric viruses. This finding suggests that vaccines designed 20 to 30 years ago to combat enteric disease associated with BoCV infection may not work to control respiratory disease associated with more recent BoCV. Similar studies are now in progress to examine changes in other respiratory viral pathogens including PI3 and BRSV. This identified a need for companies to update vaccine strains.
Impacts
(N/A)
Publications
- Bannantine, J.P., Olsen, S.C., Kehrli Jr, M.E., Stanton, T.B., Casas, E., Whipple, D.L., Zuelke, K.A. 2013. High-impact animal health research conducted at the USDA's National Animal Disease Center. Veterinary Microbiology. 165(2013):224-233.
- Bauermann, F.V., Ridpath, J.F., Weiblen, R., Flores, F.F. 2013. HoBi-like viruses - an emerging group of pestiviruses. Journal of Veterinary Diagnostic Investigation. 25(1):6-15.
- Bauermann, F.V., Harmon, A., Flores, E.F., Falkenberg, S.M., Reecy, J.M., Ridpath, J.F. 2013. In vitro neutralization against HoBi-like viruses by antiobodies in serum of cattle immunized with inactivated or modified live vaccines of bovine viral diarrhea virus 1 and 2. Veterinary Microbiology. 166(1-2):242-245.
- Jiang, Z., Zhou, X., Michal, J.J., Wu, X.-L., Zhang, L., Zhang, M., Ding, B., Liu, B., Manoranjan, V.S., Neill, J.D., Harhay, G.P., Kehrli, Jr., M.E. , Miller, L.C. 2013. Reactomes of porcine alveolar macrophages infected with porcine reproductive and respiratory syndrome virus. PLoS One. 8(3) :e59229.
- Newcomer, B.W., Marley, M.S., Ridpath, J.F., Neill, J.D., Boykin, D.W., Kumar, A., Givens, M.D. 2012. Efficacy of a novel antiviral compound to inhibit replication of multiple pestivirus species. Antiviral Research. 96(2):127-129.
- Richeson, J.T., Kegley, E.B., Powell, J.G., Schaut, R.G., Sacco, R.E., Ridpath, J.F. 2013. Weaning management of newly received beef calves with or without continuous exposure to a persistently infected bovine viral diarrhea virus pen mate: Effects on rectal temperature and serum proinflammatory cytokine and haptog. Journal of Animal Science. 91(3):1400- 1408 DOI:10.2527/jas.2011-4875.
- Schuster, G.L., Donaldson, J.R., Buntyn, J.O., Duoss, H.A., Callaway, T.R., Carroll, J.A., Falkenberg, S.M., Schmidt, T.B. 2013. Use of bioluminescent Escherichia coli to determine retention during the life cycle of the housefly, Musca domestica (Diptera: Muscidae, L). Foodborne Pathogens and Disease. 10:442-447.
- Yates, B.J., Papafragkou, E., Conrad, S.M., Neill, J.D., Ridpath, J.F., Burkhardt, W., Kulka, M., Degrasse, S.L. 2013. Surface plasmon resonance biosensor for detection of feline calicivirus, a surrogate for norovirus. International Journal of Food Microbiology. 162:152-158.
- Yilmaz, H., Altan, E., Ridpath, J.F., Turana, N. 2012. Genetic diversity and frequency of bovine viral diarrhea virus (BVDV) detected in cattle in Turkey. Comparative Immunology Microbiology and Infectious Diseases. 35:411-416.
- Fulton, R.W., Ridpath, J.F., Burge, L.J. 2012. Bovine coronaviruses from the respiratory tract: Antigenic and genetic diversity. Vaccine. 31(6):886- 892.
- McGill, J.L., Nonnecke, B.J., Lippolis, J.D., Reinhardt, T.A., Sacco, R.E. 2013. Differential chemokine and cytokine production by neonatal bovine gamma delta T cell subsets in response to viral toll-like receptor agonists and in vivo respiratory syn cytial virus infection. Immunology. 139(2):227-244.
- Sacco, R.E., McGill, J.L., Palmer, M.V., Lippolis, J.D., Reinhardt, T.A., Nonnecke, B.J. 2012. Neonatal calf infection with respiratory syncytial virus: drawing parallels to the disease in human infants. Viruses. 4(12) :3731-3753.
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Progress 10/01/11 to 09/30/12
Outputs
Progress Report Objectives (from AD-416): Objective 1: Determine the impact of variant and emerging viruses on the development and control of respiratory disease in ruminants. Develop means to detect and survey for variant viruses and develop models for evaluating infections with emerging variant viruses. Subobjectives: (1a) Determine impact of variant and emerging viruses; (1b) Improve current surveillance methods and diagnostic tools used to detect and control emerging viruses. Objective 2: Elucidate the host-pathogen interactions associated with the Bovine Respiratory Disease Complex (BRDC) by defining host pathways modulated as a result of viral infections and characterizing the role of stress and immunological related host effector molecules in BRDC. Subobjectives: (2a) Define interactions of viral pathogens that may contribute to the development of respiratory disease; (2b) Define modulation of host immune response to viral infection associated with stress caused by vitamin D insufficiency. Objective 3: Evaluate formulations and delivery systems for vaccination of neonates by identifying means to modulate stress and immunological factors associated with BRDC. Generate identification criteria and means to generate �vaccine ready� calves to develop intervention strategies for controlling viral respiratory infections of ruminants. Subobjectives: (3a) Identify factors, associated with common management practices, that modulate immune function in neonatal calves; (3b) Evaluate candidate vaccine for use in calves. Approach (from AD-416): The goal of this project is to reduce the incidence and impact of viral infections in ruminants with particular emphasis on viral infections that contribute to respiratory disease in cattle. The project encompasses three distinct but interrelated research efforts. The first is to determine the incidence and impact of variant viruses, such as subgenotypes of bovine viral diarrhea virus (BVDV), and emerging viruses, such as HoBi-like viruses, to bovine respiratory disease. The purpose of this research is to determine if new antigens, representing variant and emerging viruses, need to be included in vaccines. The second is to examine the interaction of host and virus in respiratory disease. Included in this effort will be the study of host immune dysfunction, resulting from viral infection, nutrition, or stress. The purpose of this research is to define factors that contribute to respiratory disease in order to develop means of intervention that negate or ameliorate those factors. The third is to determine means by which host resistance to viral infection can be enhanced with emphasis on improving protective innate and acquired immune responses in calves. The information generated from these three research areas will be used in the development of intervention strategies to control and eliminate viral pathogens. Improved control of viral pathogens will benefit consumers by ensuring a healthful food supply, enhance animal health and well-being, and reduce production costs for farmers and ranchers. A study comparing antigenic characteristics of Bovine viral diarrhea virus 1 and 2 (BVDV-1, -2) strains and HoBi virus was completed and the manuscript accepted for publication. The comparison was based on detection of HoBi virus and antibodies against it by commercial enzyme- linked immunosorbent assays (ELISAs) and the level of cross-neutralizing antibodies present in sera from animals vaccinated with killed BVDV. The results of this study indicate that detection and control of HoBi virus infections in cattle requires the development of new diagnostic reagents and reformulation of current vaccines. A manuscript comparing BVDV and HoBi-like virus infection of calves has been accepted for publication. In vivo studies of the impact of HoBi like infections on the immune system, including the generation of immunotolerant persistently infected cattle, have been started. BVDV isolated from bison, mountain goat and big horn sheep have been acquired and preliminary sequencing has begun. Studies of single infection of cattle with BVDV and BRSV have been completed. The transcriptomes of circulating B, T and monocyte cells of cattle infected with either high or low virulence BVDV have been generated. Models to study in vitro dual infection of cells infected with both BVDV and BRSV are under development. Studies of BVDV infection in macrophages and BRSV infection in macrophages have been completed and a manuscript has been drafted. A new component of Objective 2 will be examining host genetic markers that are associated with increased susceptibility or resistance to BRDC. Research milestones specifically addressing these contributions will be written for FY13. Accomplishments 01 Mechanism of Bovine Viral Diarrhea (BVDV) suppression of response to a secondary bacterial infection. The immune system consists of two branch the innate immune system and the acquired immune system. The innate immune system is the first line of defense against infection. One of th side effects of infection with BVDV is suppression of the immune system and it is theorized that this suppression reduces the ability of cattle fight off bacterial infections. ARS researchers at Ames, Iowa identifie specific functions of the innate immune system that are affected by BVDV infection. Identification of these functions will contribute to development of means to block viral pathology. 02 Diagnostics to detect HoBi like viruses. A newly emerging type of virus distantly related to BVDV, has been isolated from cattle in South Americ Southeast Asia and Europe. The clinical presentation following infectio with this type of virus, known as HoBi-like viruses, is very similar to that seen following infection with BVDV. Like BVDV, HoBi-like viruses cause immune suppression and can establish life long persistent infectio in cattle. HoBi like viruses have not yet been detected in the U.S. AR researchers at Ames, Iowa have developed tests to provide diagnosticians and regulatory agencies with tools to screen imported animals and animal products to prevent introduction of HoBi like viruses into the U.S. and means to detect and quickly control introduction if it does occur.
Impacts
(N/A)
Publications
- Bauermann, F.V., Flores, E.F., Ridpath, J.F. 2012. Antigenic relationships between bovine viral diarrhea virus 1 and 2 and HoBi virus: Possible impacts on diagnosis and control. Journal of Veterinary Diagnostic Investigation. 24(2):253-261.
- Hessman, B.E., Sjeklocha, D.B., Fulton, R.W., Ridpath, J.F., Johnson, B.J., McElroy, D.R. 2012. Acute bovine viral diarrhea associated with extensive mucosal lesions, high morbidity, and mortality in a commercial feedlot. Journal of Veterinary Diagnostic Investigation. 24(2):397-404.
- Montaldo, H.H., Casas, E., Sterman Ferraz, J.B., Vega-Murillo, V.E., Roman- Ponce, S.I. 2012. Opportunities and challenges from the use of genomic selection for beef cattle breeding in Latin America. Animal Frontiers. 2(1) :23-29.
- Neill, J.D. 2011. Caliciviruses. In: eLS. Chichester, UK: John Wiley & Sons, Ltd. Available:
- Richeson, J.T., Kegley, E.B., Powell, J.G., Vander Ley, B.L., Ridpath, J.F. 2012. Weaning management of newly received beef calves with or without continuous exposure to a persistently infected bovine viral diarrhea virus pen mate: Effects on health, performance, bovine viral diarrhea virus titers, and peripheral blood leukocytes. Journal of Animal Science. 90:1972-1985.
- Vander Ley, B.L., Ridpath, J.F., Sweiger, S.H. 2012. Bovine viral diarrhea virus antigen detection across whole cattle hides using two antigen- capture enzyme-linked immunoassays. Journal of Veterinary Diagnostic Investigation. 24(3):546-548.
- Zanella, R., Casas, E., Snowder, G., Neibergs, H. L. 2011. Fine mapping of loci on BTA2 and BTA26 associated with bovine viral diarrhea persistent infection and linked with bovine respiratory disease in cattle. Frontiers in Genetics. 2:82. Available:
- Ridpath, J.F., Neill, J.D., Chase, C.C. 2012. Impact of BVDV infection of white-tailed deer during second and third trimesters of pregnancy. Journal of Wildlife Diseases. 48(3):758-762.
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