Source: OHIO STATE UNIVERSITY submitted to
ZOONOTIC DISEASES IN ANIMAL AGRICULTURE: IMPLICATIONS TO PUBLIC HEALTH AND AGRIRESEARCH TO COMBAT THE PATHOGENS
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
NEW
Funding Source
ANIMAL HEALTH
Reporting Frequency
Annual
Accession No.
1018069
Grant No.
(N/A)
Project No.
OHO00005-AH
Proposal No.
(N/A)
Multistate No.
(N/A)
Program Code
(N/A)
Project Start Date
Oct 30, 2018
Project End Date
Sep 30, 2023
Grant Year
(N/A)
Project Director
Kenney, SC.
Recipient Organization
OHIO STATE UNIVERSITY
1680 MADISON AVENUE
WOOSTER,OH 44691
Performing Department
Food Animal Health Research Program
Non Technical Summary
Foodborne and waterborne diseases constitute a significant burden for public health. More than two-thirds of infectious diseases affecting humans and three-fourths of emerging human disease threats are zoonotic. Food producing animals, including poultry, serve as reservoirs for these pathogens. Furthermore, for many zoonotic diseases there are no effective vaccine or control strategies and the use of antibiotics is complicated by the emergence of resistant bacteria. Together, these public health and safety concerns underscore the critical need for integrated research efforts to better understand the ecology and epidemiology of zoonoses, pathogenesis, and immune response to these zoonotic pathogens so that effective strategies can be developed to prevent the dissemination of these organisms in the environment and limit the spread of these zoonotic agents to humans. The focus of this project will be to: 1) understand the ecology and epidemiology of zoonotic pathogens in animal reservoirs and their environment, 2) investigate the occurrence, dissemination and ecological fitness of antibiotic resistant pathogens and 3) develop and evaluate efficient methods/strategies and models for the detection and prevention of zoonotic pathogens in the farm to table continuum.
Animal Health Component
100%
Research Effort Categories
Basic
100%
Applied
(N/A)
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
3114010110030%
3114030110130%
3114030109030%
3113999104010%
Knowledge Area
311 - Animal Diseases;

Subject Of Investigation
3999 - Animal research, general; 4010 - Bacteria; 4030 - Viruses;

Field Of Science
1090 - Immunology; 1040 - Molecular biology; 1101 - Virology; 1100 - Bacteriology;
Goals / Objectives
The overall goal of this research is to combine the research expertise of the Food Animal Health Research Program to enhance the understanding of the microbiology, epidemiology and pathogenesis of zoonotic pathogens and develop effective control strategies for these infectious agents of livestock that have potential for zoonotic transmission. Towards this end, we propose to investigate the following aspects of several zoonotic pathogens for which food-producing animals serve as reservoirs.Elucidate the mechanisms of microbial pathogenesis of zoonotic pathogens of food safety, animal health and public health concerns.Understand immunity to these pathogens using animal models.Define the epidemiology and ecology of these foodborne zoonotic pathogens in the food producing animals, fresh produce and their production environments.Understand the routes of interspecies transmission of zoonotic pathogensDevelop and evaluate vaccines, therapeutics, adjuvants, and diagnostics for foodborne zoonotic pathogens.
Project Methods
Due to the wide variety of zoonotic pathogens that may emerge as potential public health threats, the specific methods will vary from individual project to project. However, our underlying strategy is to use a hypothesis-driven research approach to provide sound scientific data concerning the research problems investigated.Research may include development and/or utilization of animal models of infection to characterize mechanisms of pathogenesis and pathogen/host interactions. These include studies of pathogenesis and comparative pathogenesis, interspecies transmission of pathogens, understanding the molecular basis of pathogenesis, studies of pathogen and host gene expression and characterization of host genetic risk factors for disease susceptibility.We will exploit current advances in the detection of gene and protein expression patterns to assess disease progression, and to seek unique host cellular signatures indicative of infection and/or protective immune responses. Studies of the natural rates of horizontal gene transfer, especially of plasmid-encoded toxins and antibiotic resistance factors, in the microbial ecosystems likely to be most exposed to foodborne pathogens.For the studies on epidemiology of infections in natural non-human and human hosts, we will use extensive in-field sampling strategies coupled with epidemiological practices targeted at identifying factors that influence the distribution, acquisition, course and severity of human disease. This will also include studies on pathogens in the environment and non-food-producing vectors, when those studies may contribute to the understanding of factors bearing on emergence, transmission, persistence, development of virulence, host switching, and/or epidemic/epizootiologic thresholds as they directly pertain to human disease.The unique gnotobiotic and specific pathogen free animal facilities (piglets and calves) available at the FAHRP will be used to study the microbial community population structure, metatranscriptomics, metabolomics and impact of probiotic or prebiotic or symbiotic interventions for infectious diseases using these animals as models. This approach has provided researchers with the unparalleled opportunity to discover how diet and bacterial populations in newborn animals modulate and influence the animals' response to infection.For food safety studies, targeting each specific group of individuals (producers) with tailored food safety messages that address their biases and pre-existing beliefs will enhance adoption and assist them in making more informed decisions about their health. This mental model approach to message development and delivery can be applied to a variety of topics and will enhance the effectiveness of other outreach and engagement activities.

Progress 10/01/19 to 09/30/20

Outputs
Target Audience:The target audiences are agricultural constituents and researchers within Ohio, the United States and worldwide. Changes/Problems:The primary issues are related to the ongoing COVID-19 pandemic. Laboratory personnel restrictions, inability to raise and perform animal experiments, inability to hire new personnel have all significantly contributed to research delays from April 2020 and continue through December 2020 and into the next reporting period. What opportunities for training and professional development has the project provided?The laboratories encompassed by PIs affiliated with this grant include at least 14 graduate students, 4 postdoctoral scholars, and 3 visiting scholars along with research support staff and animal care workers. Additionally, there have been several undergraduate volunteers who have participated in projects in the laboratories. Exemplary trainings include: A graduate student from Ethiopia was trained for a year about microbiology (selective media, growing condition, and bio-banking) and bio-molecular (DNA extraction, conventional PCR, viability PCR, and real-time PCR) approaches, and statistical tools (Excel and JMP Pro14) used to detect, isolate, quantify, and identify thermophilic and non-thermophilic Campylobacter at the genus and species level from different field sample types (skin, milk, feces, soil, water, food, and fomites). Similarly, the student learnt microbiological techniques to detect, isolate and quantify coliforms and E. coli from the same field samples. A student from Columbia completed her master's work on bioinformatic analysis applied to studying infectious transmission factors. A student from Nepal completed his master's thesis on molecular virology aspects of hepatitis E virus (HEV)while completing essential testing of proprietary technology used to inactivate HEV in blood prior to transfusion. Four graduate students, 2 postdoctoral scholars, 2 research associates, and 3 faculty members were trained and certified to perform BSL-3 experiments in the Plant and Agrosecurity Research (PAAR) facility. Students have been taught to prepare research papers for submission to peer reviewed journals Numerous students have been taught how to prepare and submit abstracts for trade and international meetings as well as present their research (Although in a much more virtual format than in previous years.) How have the results been disseminated to communities of interest?Dissemination of research findings are primarily communicated via research article published in peer reviewed journals. Presentations and abstracts given at professional meetings. In addition, faculty meet with constituent groups and perform outreach and extension with constituents and talks to young students. Some content has been digitized for presentation at the 2020 CFAES Farm Science Review online. What do you plan to do during the next reporting period to accomplish the goals?Influenza: Lee lab will optimize high throughput screening methods using cell line that reports the activation of interferons for the selection and development of live attenuated influenza vaccines with strong immunostimulatory properties and increased the breadth of the immunity. Gourapura lab is onboarding several new postdoctoral scholars and graduate students. Research towards rationally designed nanoparticle vaccines for inducing mucosal immunity against SARS-CoV-2 as well as other emerging coronaviral pathogens will continue. Improvement of nanoparticle vaccine platforms for influenza viruses will also continue. SARS-CoV-2/COVID19 Saif/Vlasova/Wang/Kenney laboratories are onboarding additional students, postdoctoral researchers, and visiting scholars to continue pursuing aspects relating to COVID19 disease, vaccine development, and cross specie transmission. Expanding current serological research to larger numbers of patients, to evaluate the extent of immunological cross-reactivity between SARS-CoV-2 and other human coronaviruses associated with common colds, and to evaluate the role of these cross-reactive antibodies in SARS-CoV-2 pathogenesis and immunity. Continuing to compare cross species transmission factors between differing coronavirus species utilizing bioinformatics approach. Attempting to secure funding to examine the role of porcine deltacoronavirus in human disease via an epidemiological screening approach. Bacterial Diseases The Rajashekara lab is continuing to train graduate students on several different bacterial species known to transmit from animals to humans. Continued development of small molecule inhibitors that can prevent the spread of disease to humans though the food supply.

Impacts
What was accomplished under these goals? Influenza virus:The Lee laboratory's primary focus was: Development of in vitro viral subpopulation-based screening for the selection of high interferon inducing live attenuated influenza vaccine. Live attenuated influenza vaccines with truncations in non-structural protein 1 (NS1) have shown broad protective efficacies in birds and mammals, which correlate with the ability to induce elevated interferon responses in the vaccinated hosts. We asked if we could improve an NS1-truncated live attenuated influenza vaccine developed for poultry (PC4) by selecting viral subpopulations with enhanced interferon-inducing capacities. In this study, we deconstructed a de novo population of PC4 through plaque isolation, created a large library of clones, and assessed their interferon-inducing phenotypes. While most of the clones displayed the parental interferon-inducing phenotype in cell culture, few clones showed enhanced interferon-inducing phenotypes in cell culture and chickens. The enhanced interferon-inducing phenotypes were linked to either a deletion in NS1 (NS1Δ76-86) or a substitution in polymerase basic 2 protein (PB2-D309N). The NS1Δ76-86 deletion disrupted the putative eukaryotic translation initiation factor 4GI-binding domain and promoted the synthesis of biologically active interferons. The PB2-D309N substitution enhanced the early transcription of interferon mRNA, revealing a novel role for the 309D residue in suppression of interferon responses. We combined these mutations to engineer a novel vaccine candidate that induced additive amounts of interferons and stimulated protective immunity in chickens. We demonstrated that viral subpopulation screening approaches can guide the design of live vaccines with strong immunostimulatory properties. The newly developed in vitro interferon-based pipeline for live vaccine discovery has potential to increase the number of vaccine candidates subjected to the screening process, reduce the number of animals subjected to efficacy trials and cutting the time and cost associated with formulation and production of vaccines. The Gourapura laboratory developed corn nanoparticle (Nano-11) adsorbed inactivated swine influenza A virus (SwIAV) and Poly (I:C) adjuvanted [Nano-11-KAg+Poly(I:C)] vaccine to augment mucosal immune responses in maternal derived antibody (MDA) positive pigs. Our data indicated that Nano-11-KAg+Poly(I:C) vaccine delivered intranasal stimulated robust cross-reactive IgG and secretory IgA antibodies in the lungs and broadly protective polyfunctional cell-mediated immune responses to highly variant SwIAV, associated with reduction in viral load in the airways and amelioration of lung pathology comparable to a multivalent commercial vaccine. But the commercial vaccine appears to elicit a strong inflammatory response associated with accumulation of naïve T-helper cells in both the mucosal lymph nodes and systemic compartment suggesting possible inefficient antigen presentation in MDA positive pigs. They also developed mannose conjugated chitosan nanoparticle delivered monovalent inactivated SwIAV (mCS NPs-KAg) vaccine. The mannose conjugation in the candidate vaccine increased the specific recall lymphocyte proliferation, late effector and effector memory cells population, IFNγ secreting CTLs and cytokine gene expression resulting in reduced heterologous challenge virus infection. Overall, their studies suggested that mCS NPs-KAg vaccine could be a useful and effective alternative to commercial influenza vaccine for inducing cross-protective immunity against SwIAV in MDA-positive grow-finisher pigs. Coronaviruses including SARS-CoV-2/COVID19 and other emerging pathogens:Recently we initiated ongoing efforts to develop SARS-CoV-2 specific ELISA for detailed characterization of humoral immunity to SARS-CoV-2 infection and vaccination as a part of the establishment of the OSU SeroNet Center of Excellence - the Center for Sero-genetic Testing to Improve Outcomes from COVID-19 (STOP COVID), recently funded by the NCI/NIH U54 program. The labs of Saif/Wang/Vlasova, and Kenney have established and are currently validating SARS-CoV-2 peptide-based ELISA. Preliminary screening of a small number of human samples (N=80) demonstrated that severe COVID19 cases have higher SARS-CoV-2 specific antibody responses irrespective of the disease stage. Members of the labs have been trained to work at BSL3 and BSL3-Ag facilities. Since June, we have isolated Ohio SARS-CoV-2 strains, established plaque reduction neutralization test and other basic assays, generated an infectious clone for SARS-CoV-2, and performed cold-adaptation of SARS-CoV-2 for the development of live attenuated vaccines. During the late 2019 and early 2020 research cycle we accomplished to following research despite being hampered by COVID-19 work restrictions. Developed a luminescent immunoprecipitation assay (LIPS) for serological detection of PDCoV in in pigs with >95% specificity. Established a LIPS assay specific for SARS-CoV-2 and confirmed that it did not react with serum from animals infected with SARS-CoV-1, PEDV, TGEV, PDCoV, or Canine coronavirus. Created a viral neutralizing pseudovirus assay for SARS-CoV-2 to confirm ELISA and LIPS results and in testing potential SARS-CoV-2 vaccines for neutralizing titers. The Kenney laboratory has published results demonstrating PDCoV can cross species barriers to infect chickens and turkeys. We have established global transcription changes in pig and human cells during PDCoV infection utilizing RNAseq. Developed LIPS assay specific for SARS-CoV-2. Assay was confirmed to not react with serum from animal infected with SARS-CoV-1, PEDV, TGEV, PDCoV, Canine coronavirus. Currently screening serum samples from various species in Ohio. Developed viral neutralizing pseudovirus assay for SARS-CoV-2 to confirm ELISA and LIPS results. Also, for use in testing potential SARS-CoV-2 vaccines. Published results demonstrating PDCoV can infect chickens and turkeys. Pathology revealed PDCoV can cause mild gastroenteritis in chickens with more moderate damage in turkeys, but no mortality was observed. Salmonella The Rajashekara laboratory identified three probiotic derived peptides that completely inhibit the growth of multiple Salmonella serotypes by disrupting their cell membrane integrity. One of these peptides inhibited the growth of Salmonella Typhimurium in broiler chickens (approx. 2-log reduction). We identified three probiotic derived peptides that completely inhibit the growth of multiple Salmonella serotypes by disrupting their cell membrane integrity. One of these peptides inhibited the growth of Salmonella Typhimurium in broiler chickens (approx. 2-log reduction). Campylobacter jejuni Rajashekara lab identified two novel narrow spectrum Campylobacter specific small molecule growth inhibitors having MIC of less than 50 μM with restricted effects on other prokaryotes. The compounds reduced C. jejuni burden in broiler chicken's ceca when treated for 5 days with 100 g/chicken and had minimal impact on the cecal microbiota. We assessed the prevalence and abundance of Campylobacter spp. in young children stools (n=100) from eastern Ethiopia and its association with the stool microbiome, environmental enteric dysfunction (EED) and diarrhea status of the children. High prevalence in Campylobacter (88%) and high species diversity (n=39) were detected in the children stools collected from Ethiopia. Further, we observed that the Campylobacter prevalence, EED severity, and diarrhea status had an impact on the stool microbiome profile.

Publications

  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Calisher, C. L.J. Saif, et al. 2020.Statement in support of the scientists, public health professionals, and medical professionals of China combatting COVID-19. Lancet. Published Online February 18, 2020 https://doi.org/10.1016/
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Liu, S-L, L. J. Saif, S.R. Weiss and L. Su. 2020. No credible evidence supporting claims of the laboratory engineering of SARS-CoV-2. Emerging Microbes &Infections, 9:1, 505-507, DOI: 10.1080/22221751.2020.1733440.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Saif, L.J. ASM COVID-19 Research Registry Invited Commentary, Nov 6, 2020, The effect of infuenza vaccination on trained immunity: impact on COVID-19 by P. A. Debisarun, et al. medRxiv 2020.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Saif, L.J. ASM COVID-19 Research Registry Invited Commentary, May 15, 2020, Trinity of COVID-19: Immunity, inflammation and intervention by Tay, M.Z., et al, Nat Rev Immunol
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Renu, S, N. Feliciano-Ruiz, S. Ghimire, Y. Han, J. Schrock, S. Dhakal, V. Patil, S. Krakowka and G.J. Renukaradhya* (2020). Poly(I:C) augments inactivated influenza virus-chitosan nanovaccine induced cellular immune response in intranasal vaccinated pigs. Vet Microbiology, 242:108611. PMID: 32122615. IF  2.524.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Hiremath, J, K. Tabynov and G.J. Renukaradhya* (2020). Pulmonary Inflammatory Response to Influenza Virus Infection is regulated by DAP12 and macrophage M1 and M2 phenotypes: a study in a porcine model. Cellular Immunology, 352:104078. PMID: 32164997
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Renu, S, N. Feliciano-Ruiz, F. Lu, S. Ghimire, Y. Han, J. Schrock, S. Dhakal, V. Patil, S. Krakowka, H. HogenEsch and G.J. Renukaradhya* (2020). A Nanoparticle-Poly(I:C) Combination Adjuvant Enhances the Breadth of the Immune Response to Inactivated Influenza Virus Vaccine in Pigs. Vaccines (Basel), 8(2): E229. PMID: 32443416. IF  4.086.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Renukaradhya, G.J* (2019). Acute inflammation and influenza: Innovative nanoparticle vaccination studies in a pig model. Indian Journal of Inflammation Research
  • Type: Journal Articles Status: Accepted Year Published: 2019 Citation: Dhakal S and G.J. Renukaradhya* (2019). Nanoparticle-based vaccine development and evaluation against viral infections in pigs. Veterinary Research, 50(1):90. PMID: 31694705. IF  3.357.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Renu, S and G.J. Renukaradhya* (2020). Chitosan nanoparticle based mucosal vaccines delivered against infectious diseases of poultry and pigs. Front Immunol., 11:935. PMID: 32508828. IF  5.085.
  • Type: Journal Articles Status: Under Review Year Published: 2020 Citation: Yada KK, Boley PA, Fritts Z, Kenney SP. Genotype 1 hepatitis E virus (HEV) ORF4 protein enhances genotype 3 HEV replication. Under Review Journal of Virology
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Ghorbani A, Abundo MC, Ji H, Taylor KJM, Ngunjiri JM, Lee CW. Viral Subpopulation Screening Guides in Designing a High Interferon Inducing Live Attenuated Influenza Vaccine by Targeting Rare Mutations in NS1 and PB2 Proteins. Journal of Virology. JVI.01722-20. doi: 10.1128/JVI.01722-20. Online ahead of print. 2020.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Ghorbani A, Ngunjiri JM, Lee CW. Influenza A Virus Subpopulations and Their Implication in Pathogenesis and Vaccine Development. Annu Rev Anim Biosci. 8:247-267. 2020.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Stephanie N. Langel *, Qiuhong Wang, Anastasia N. Vlasova, Linda J. Saif *. 2020. Host factors affecting generation of immunity against porcine epidemic diarrhea virus in pregnant and lactating swine and passive protection of neonates. Pathogens. 9(2):130. DOI: 10.3390/pathogens9020130 (Review)
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Kwonil Jung*, Qiuhong Wang*, and Linda J. Saif*. Porcine epidemic diarrhea virus (PEDV): An update on etiology, transmission, pathogenesis, and prevention and control. Virus Research. 286:198045. doi: 10.1016/j.virusres.2020.198045 (review
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Saif, L.J. and K. Jung. 2020. Comparative pathogenesis of bovine and porcine respiratory coronaviruses in the animal host species and SARS-CoV-2 in humans. 58:e01355-20.https://doi.org/10.1128/JCM.01355-20
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Boley, P.A., M.A. Alhamo, G. Lossie, K.K. Yadav, M.V. Lee, L.J. Saif and S.P. Kenney. 2020. Porcine deltacoronavirus infection and transmission in poultry, United States. Emerging Infectious Diseases 26(2): 255-264.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Saif, LJ. 2020. Vaccines for COVID-19: Perspectives, prospects and challenges based on candidate SARS and MERS and animal coronavirus vaccines. EMJ. DOI/10.33590/emj/200324.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: N Decaro, V Martella, LJ Saif, C. Buonavogliaa. 2020. COVID-19 from veterinary medicine and one health perspectives: What animal coronaviruses have taught us.2020. Res Vet Sci 131:21-23. https://doi.org/10.1016/j.rvsc.2020.04.009
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: C. Zeng J. P. Evans, R. Pearson, P. Qu, Y-M Zheng, R. T. Robinson, L. Hall-Stoodley, J. Yount, S. Pannu, R. K. Mallampalli, L. J. Saif, E. Oltz, G. Lozanski, and S-L. Liu. 2020. Neutralizing antibody against SARS-CoV-2 spike in COVID-19 patients, health care workers and convalescent plasma donors: a cohort study using a rapid and sensitive high-throughput neutralization assay. JCI Insight. https://doi.org/10.1172/jci.insight.143213
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: R. A.P.M Perera, J. S. M. Peiris, R. Ko, O. Tsang, D. Hui, M. Kwan, C. Brackman, E. To, HL. Yen, K. Leung, K. Chan, K.Chan, KC. LI, L. Saif, V. Barrs, J. Wu, T. Sit, L. Poon, and S. Cheng. Evaluation of a SARS-CoV-2 surrogate virus neutralization test for detection of 2 antibody in human, canine, cat and hamster sera. J Clin Microbiol (in press).
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Makoto Nagai, Qiuhong Wang*, Tomoichiro Oka, and Linda J. Saif. 2020. Porcine sapoviruses: Pathogenesis, epidemiology, genetic diversity, and diagnosis. Virus Research. 286:198025. https://doi.org/10.1016/j.virusres.2020.198025 (review)
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Hirotaka Takagi *, Tomoichiro Oka *, Hiroyuki Saito, Takayuki Kobayashi, Tomoko Takahashi, Chika Tatsumi, Takashi Shimoike, Michiyo Kataoka, Qiuhong Wang*, Linda J. Saif*, Mamoru Noda. Human sapovirus propagation in human cell lines supplemented with bile acids. PNAS (in press)
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Yusheng Guo, David E. Wentworth, Karla M. Stucker, Rebecca A. Halpin, Ham C. Lam, Douglas Marthaler, Linda J. Saif, Anastasia N. Vlasova. 2020. Amino Acid Substitutions in Positions 385 and 393 of the Hydrophobic Region of VP4 May Be Associated with Rotavirus Attenuation and Cell Culture Adaptation. Viruses. 2020 Apr 7;12(4):408. doi: 10.3390/v12040408.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Michael, H., S.N. Langel, A. Miyazaki, D.D. Fischer, V. Srivastava, D. Kathayat, L. Deblais, G. Rajashekara, L.J. Saif and A.N. Vlasova. 2020. Malnutrition decreases antibody secreting cell numbers induced by an oral attenuated human rotavirus vaccine in a human infant fecal microbiota transplanted gnotobiotic pig model. Front.Immunol.11:196.doi:10.3389/?mmu.2020.00196.
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Srivastava, V., L. Deblais, H.C. Huang, A.N. Vlasova, A. Miyazaki, S. Kandasamy, S.N. Langel, F.C. Paim, J. Chepngeno, D. Kathayat, L.J. Saif and G. Rajashekara. 2020. Protein malnutrition affects the rotavirus vaccine efficacy by modulating the gut microbiota composition in a fecal microbiota transplanted gnotobiotic pigmodel. Beneficial Microbes (in press)
  • Type: Journal Articles Status: Accepted Year Published: 2020 Citation: Wu, Y., Ho, W., Huang, Y., Jin, D.Y., Li, S., Liu, S.L., Liu, X., Qiu, J., Sang, Y., Wang, Q., Yuen, K.Y., Zheng, Z.M., 2020. SARS-CoV-2 is an appropriate name for the new coronavirus. Lancet 395, 949-950.


Progress 10/30/18 to 09/30/19

Outputs
Target Audience:The Food Animal Health Research Program (FAHRP) and the College of Food Agriculture and Environmental Sciences (CFAES) maintains a strong commitment to informing constituents, contributing to cutteing edge research, and training the next generation of agriculturists and scientists. We have continued fulfilling this mission throughout the past year, in part, utiliizing the funds provided through this funding mechanism. The primary audience shown by documented publications is the greater scientific community. Through publication in peer reviewed journals our research is made publicly available to our peer institutions, otherscientists, students, and the general public. In addition to publication of peer reviewed articles the entire faculty of FAHRP is actively engaged in attending and presenting their newest findings at scientific conferences. Meetings such as The American Society for Virology, Conference for Researcher Workers in Animal Diseases, North American PRRSV, Tri State Veterinary Poultry Association Meeting, Nidovirales, Midwest Virology Symposium, International Hepatitis E Virus Symposium, among others were highly attended by FAHRP faculty. These meetings allow for direct interaction of FAHRP faculty with peer scientists and interested individuals, such as poultry veterinarians, state veterinarians, members of the USDA and NIFA, etc. FAHRP continues making an impact withregional agriculturalists through outreach and extension activities. As they have done for many years, FAHRP faculty took part in the Farm Science Review in London, OH where they presented material relevant to food safety and vaccination to the hundreds of participants attending the agricultural show. In addition, faculty have been establishing ties with local primary schools to aid in presenting microbiology based science, technology, engineering, and mathematics (STEM)based programming to middle school aged children. The FAHRP faculty will continue their efforts to reachthe broadestrelevant constituency to ensure the highest impact stemming from their research activities. Changes/Problems:We do not see any major changes or problems in our approach. The overall goals of the project are written sufficiently broadly to cover the existing research programs within FAHRP. The inclusion of 8 different faculty members enables us to achieve positive goals even in the event that an individual member may be struggling at any given time. As it stands, each investigator and co-investigator has made significant contributions to the overall project goals. Extramural funding for several project members has been obtained and they will continue their research progress as stated. Other faculty members continue to seek funding and as such, their research goals will be in line with the obtained funding. We are hopeful that 2020 will prove as productive as 2019 for FAHRP and the whole of CFAES. What opportunities for training and professional development has the project provided?FAHRP is primarily a research based department focused on professional training of graduate and post graduate scholars. Projects by each faculty member and funding from many different granting agencies has led to numerous opportunities for training these students. Currently the department has 15vgraduate students, 5 postdocs, and 5 visiting scientists. This number fluctuates based on graduation and recruitment thoughout the year. There is no shortage of ideas to provide additional training opportunities for these students. We are only limited by the number of available faculty and extramural funding to support these types of educational opportunities. How have the results been disseminated to communities of interest?As alluded to in target audience, FAHRP is dedicated to bestowing our experimental knowledge to the general public. We have a very successful track record in publiching our results in high impact peer reviewed journals for knowledge dissemination to professional colleagues and other agricultural, veterinay, and medicalinstitutions. FAHRP faculty have been very active in regional, national, and international professional meetings where results are shared with pertinent professionals and the general public. We have extensive speaking engagements at other universities, both domestic and foreign. FAHRP participates in otreach and extension activities through booths at the Farm Science Review, county fairs, and preparing curriculum for constituents on the merits of food safety, vaccination, and animal health topics. What do you plan to do during the next reporting period to accomplish the goals?We will study how to develop recombination-resistant live attenuated vaccines for PEDV by manipulating the viral transcription regulation signal. Using the reverse genetics platform of PDCoV, we will investigate the mechanisms of interspecies transmission of PDCoV. We will look for nontoxic and economic inhibitors to block human norovirus binding to lettuce to reduce the transmission of human norovirus via leafy greens. We will continue to adapt human sapoviruses in routine cell culture. Continue epidemiological surveillance to examine: If δ-CoV prevalence and diversity increases over time and if there are avian δ-CoVs more closely related to swine δ-CoVs. Inoculate Gn piglets with avian δ-CoVs to determine if a productive infection is established We will conduct further studies to evaluate the molecular mechanisms behind the increased pathogenicity of novel porcine RVC strains and to identify means to boost protective lactogenic immunity against RVC. We will validate the trends observed on the effects of vitamin A deficiency/supplementation on immune responses and mucosal trafficking in PEDV seronegative/RV seropositive uninoculated gestating and lactating sows. We will evaluate how probiotic protective efficacy against different RV genotypes is affected by the tripartite histo-blood group antigen-RV-probiotic interactions. We will examine the ability of recombinantδ-CoVs to alter pathogenicity in avian species. We will continue to explore the roles of Hepatitis E virus ORF4 in enhancing pregnancy associated mortality. We will evaluate the prevalence of exposure to porcine δ-CoVs among the general population. We will continue to evaluate nanoparticle based adjuvants for efficacy against many emerging agricultural pathogens. We will continue to seek extramural support to fund training activities.

Impacts
What was accomplished under these goals? 1. Elucidate the mechanisms of microbial pathogenesis of zoonotic pathogens of food safety, animal health and public health concern. We assessed the prevalence and abundance of Campylobacter spp. in young children stools (n=100) from eastern Ethiopia and its association with the stool microbiome, environmental enteric dysfunction (EED) and diarrhea status of the children. High prevalence in Campylobacter (88%) and high species diversity (n=39) were detected in the children stools collected from Ethiopia. Further, we observed that the Campylobacter prevalence, EED severity, and diarrhea status had an impact on the stool microbiome profile. We comparatively assessed the pathogenesis of more recent (2012) and historic (1980) porcine rotavirus C strains in 3-day- and 3-week-old gnotobiotic piglets. We demonstrated that the current and historic RVC strains possess distinct pathobiological characteristics, with a newer strain inducing more severe clinical disease and higher virus replication combined with decreased IgA antibody responses. New porcine epidemic diarrhea virus (PEDV) variants, with a large deletion in the N-terminal domain of the S1 subunit of spike (S) protein and designated as S1 NTD-del PEDVs, emerged in the field. They replicate in experimentally infected pigs. However, on farms they often co-infect pigs with the PEDV strains containing an intact S protein (S-intact PEDV). We characterized viral replication and pathogenesis in neonatal gnotobiotic pigs infected simultaneously with the two types of PEDV. We found that S-intact PEDV replicated to a higher peak titer when pigs were co-infected with S1 NTD-del PEDV. We established porcine small intestinal enteroids (PIEs) expressing different histo-blood group (HBGAs; A+, H+ and A+/H+) to evaluate if virulent and attenuated rotavirus A (RVA) strains of various genotypes replicated more or less efficiently depending on the HBGA type. We demonstrated that replication of virulent but not attenuated RVA strains in PIEs was significantly affected by the HBGA type. We have indentified the Hepatitis E virus ORF 4 protein as a cross strain replication enhancer. 2. Understand immunity to these pathogens using animal models. We evaluated if vitamin A (VA) supplementation of porcine epidemic diarrhea virus (PEDV)-infected pregnant gilts would enhance the gut-mammary gland-secretory IgA axis to boost lactogenic immunity and passive protection of nursing piglets against PEDV. Our results demonstrated that the VA-supplemented PEDV-infected gilts protected their piglets against PEDV challenge more efficiently than the non-VA supplemented gilts. Contributed to the understanding ofCD8+ lymphocytes required for protection against chronic hepatitis E virus infection in chickens. Evaluatedcorn-derived alpha-D-glucan nanoparticles as adjuvant for intramuscular and intranasal immunization in pigs 3.Define the epidemiology and ecology of these foodborne zoonotic pathogens in the food producing animals, fresh produce and their production environments. We comparatively assessed the prevalence of δ- and γ-CoVs in wild migratory terrestrial and aquatic birds in Arkansas, Illinois, Indiana, Maryland, Mississippi, Missouri, Ohio, Tennessee and Wisconsin in 2015-2018. We demonstrated that δ-CoV are less prevalent than γ-CoVs and that both δ- and γ-CoVs occurred more frequently in aquatic birds. For the first time, we identified HKU20-like δ-CoVs in the US Contributed to the identification ofan unknown agent antigenically related to the hepatitis E virus in dairy cows in the United States. Suggests that serological identification of a potential zoonotic agent may be more difficult than expected. Identification ofa very virulent infectious bursal disease virus in New York, USA 4.Understand the routes of interspecies transmission of zoonotic pathogens We identified avian species including chickens and turkeys as susceptible to porcine deltacoronavirus infection. Suggesting these animals could be important transmission vectors or reservoirs for disease. 5.Develop and evaluate vaccines, therapeutics, adjuvants, and diagnostics for foodborne zoonotic pathogens. We identified two novel narrow spectrum Campylobacter specific small molecule growth inhibitors having MIC of less than 50 μM with restricted effects on other prokaryotes. The compounds reduced C. jejuni burden in broiler chicken's ceca when treated for 5 days with 100 mg/chicken and had minimal impact on the cecal microbiota We evaluated the Campylobacter colonization in chickens vaccinated with six Recombinant Attenuated Salmonella Vaccines (RASVs). The chickens were challenged with a cocktail of 5 chicken origin C. jejuni strains. Preliminary studies showed promising results with some vaccines with reduction in cecal Campylobacter load Porcine deltacoronavirus (PDCoV) is an emerging enteric virus of pigs that causes severe diarrhea in neonatal pigs. We generated an infectious clone of PDCoV (icPDCoV) and experimentally infected neonatal gnotobiotic pigs with it. We confirmed that its virulence was similar to that of wild type PDCoV. We generated a live attenuated PEDV vaccine candidate by inactivating the 2'-O methyltransferase (2'-O MTase) activity of nsp16 and the endocytosis signal of the spike protein using reverse genetics technology We have developed a luminescent immunoprecipitation assay for serological detection of PDCoV infection in mammalian species. We studied the effect of tryptophan (Tryp) and the probiotic Escherichia coli Nissle 1917 (EcN) as dietary supplements on the gut microbiota of HIFM transplanted Gn pigs fed with deficient diet (malnourished) and challenged with HRV. Both Tryp and EcN treatments reduced diarrhea severity and viral shedding, and improved the body weight gain and gut microbiota composition of treated pigs compared to not treated group. Both treatments increased the abundance of beneficial bacteria (i.e. Enterococcus, Bifidobacterium, and Bacteroides) and decreased the abundance of inflammation-associated bacteria (i.e. Halomonas and Shewanella). We identified three novel SM growth inhibitors (GI) with potent anti-APEC efficacy in chickens. These GI's significantly reduced the APEC induced mortality of chickens, APEC load and APEC lesions severity in chickens. We also identified two probiotics and their derived small peptides (P-1, P-2, and P-3) with antimicrobial activity against APEC. We identified quorum sensing inhibitor (QSI) that significantly reduced mortality, lesions and APEC load in the internal organs. QSI provided better protection against APEC at the lower dosage compared antibiotic (sulfonamide) currently used to treat colibacillosis in chickens. We have generated an HEV ORF4 expressing liver cell line for enhancing tissue culture growth of HEV field strains.

Publications

  • Type: Journal Articles Status: Published Year Published: 2019 Citation: The Current Host Range of Hepatitis E Viruses. Kenney SP. Viruses. 2019 May 17;11(5). pii: E452. doi: 10.3390/v11050452. Review. PMID: 31108942
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Emerging and re-emerging coronaviruses in pigs. Wang Q, Vlasova AN, Kenney SP, Saif LJ. Curr Opin Virol. 2019 Feb;34:39-49. doi: 10.1016/j.coviro.2018.12.001. Epub 2019 Jan 14. Review. PMID: 30654269
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: CD8+ lymphocytes but not B lymphocytes are required for protection against chronic hepatitis E virus infection in chickens. Rogers E, Todd SM, Pierson FW, Kenney SP, Heffron CL, Yugo DM, Matzinger SR, Mircoff E, Ngo I, Kirby C, Jones M, Siegel P, Jobst P, Hall K, Etches RJ, Meng XJ, LeRoith T. J Med Virol. 2019 Nov;91(11):1960-1969. doi: 10.1002/jmv.25548. Epub 2019 Jul 25. PMID: 31317546
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Evidence for an unknown agent antigenically related to the hepatitis E virus in dairy cows in the United States. Yugo DM, Cossaboom CM, Heffron CL, Huang YW, Kenney SP, Woolums AR, Hurley DJ, Opriessnig T, Li L, Delwart E, Kanevsky I, Meng XJ. J Med Virol. 2019 Apr;91(4):677-686. doi: 10.1002/jmv.25339. Epub 2018 Oct 31.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Hepatitis E Virus: Animal Models and Zoonosis. Kenney SP, Meng XJ. Annu Rev Anim Biosci. 2019 Feb 15;7:427-448. doi: 10.1146/annurev-animal-020518-115117. Epub 2018 Oct 4. PMID: 30285462
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Oral vitamin A supplementation of porcine epidemic diarrhea virus infected gilts enhances IgA and lactogenic immune protection of nursing piglets. Langel SN, Paim FC, Alhamo MA, Lager KM, Vlasova AN, Saif LJ. Vet Res. 2019 Nov 29;50(1):101. doi: 10.1186/s13567-019-0719-y. PMID: 31783923
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Dhakal S, Lu F, Ghimire S, Renu S, Lakshmanappa YS, Hogshead BT, Ragland D, Hogen Esch H, Renukaradhya GJ. Corn-derived alpha-D-glucan nanoparticles as adjuvant for intramuscular and intranasal immunization in pigs. Nanomedicine. 2019 Feb;16:226-235. doi: 10.1016/j.nano.2018.12.003. Epub 2019 Jan 3. PubMed PMID: 30611772
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Zhugunissov K, Bulatov Y, Taranov D, Yershebulov Z, Koshemetov Z, Zhunushov A, Renukaradhya GJ, Tabynov K, Abduraimov Y. Corrigendum to 'Beta-propiolactone inactivated bivalent bluetongue virus vaccine containing montanide ISA-71VG adjuvant induces long-term immune response in sheep against serotypes 4 and 16 even after 3 years of controlled vaccine storage' [Vet. Microbiol. 226 (2018) 23-30]. Vet Microbiol. 2019 Mar;230:291. doi: 10.1016/j.vetmic.2019.01.015. Epub 2019 Jan 23. PubMed PMID: 30683303
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Nurpeisova A, Kassenov M, Rametov N, Tabynov K, Renukaradhya GJ, Volgin Y, Sagymbay A, Makbuz A, Sansyzbay A, Khairullin B. Analysis of the efficacy of an adjuvant-based inactivated pandemic H5N1 influenza virus vaccine. Arch Virol. 2019 Apr;164(4):1027-1036. doi: 10.1007/s00705-019-04147-7. Epub 2019 Feb 10. PubMed PMID: 30740636
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: How the gut microbiome regulates host immune responses to viral vaccines. Vlasova AN, Takanashi S, Miyazaki A, Rajashekara G, Saif LJ. Curr Opin Virol. 2019 Aug;37:16-25. doi: 10.1016/j.coviro.2019.05.001. Epub 2019 Jun 1. Review. PMID: 31163292
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Engineering a Live Attenuated Porcine Epidemic Diarrhea Virus Vaccine Candidate via Inactivation of the Viral 2'-O-Methyltransferase and the Endocytosis Signal of the Spike Protein. Hou Y, Ke H, Kim J, Yoo D, Su Y, Boley P, Chepngeno J, Vlasova AN, Saif LJ, Wang Q. J Virol. 2019 Jul 17;93(15). pii: e00406-19. doi: 10.1128/JVI.00406-19. Print 2019 Aug 1. PMID: 31118255
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Stage of Gestation at Porcine Epidemic Diarrhea Virus Infection of Pregnant Swine Impacts Maternal Immunity and Lactogenic Immune Protection of Neonatal Suckling Piglets. Langel SN, Paim FC, Alhamo MA, Buckley A, Van Geelen A, Lager KM, Vlasova AN, Saif LJ. Front Immunol. 2019 Apr 24;10:727. doi: 10.3389/fimmu.2019.00727. eCollection 2019. PMID: 31068924
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Rotavirus C: prevalence in suckling piglets and development of virus-like particles to assess the influence of maternal immunity on the disease development. Chepngeno J, Diaz A, Paim FC, Saif LJ, Vlasova AN. Vet Res. 2019 Oct 22;50(1):84. doi: 10.1186/s13567-019-0705-4. PMID: 31640807
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Dhakal S, Renukaradhya GJ. Nanoparticle-based vaccine development and evaluation against viral infections in pigs. Vet Res. 2019 Nov 6;50(1):90. doi: 10.1186/s13567-019-0712-5. Review. PubMed PMID: 31694705; PubMed Central PMCID: PMC6833244.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Infectivity of GII.4 human norovirus does not differ between T-B-NK+ severe combined immunodeficiency (SCID) and non-SCID gnotobiotic pigs, implicating the role of NK cells in mediation of human norovirus infection. Annamalai T, Lu Z, Jung K, Langel SN, Tuggle CK, Dekkers JCM, Waide EH, Kandasamy S, Saif LJ. Virus Res. 2019 Jul 2;267:21-25. doi: 10.1016/j.virusres.2019.05.002. Epub 2019 May 2. PMID: 31054932
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Elaish M, Xia M, Ngunjiri JM, Ghorbani A, Jang H, Kc M, Abundo MC, Dhakal S, Gourapura R, Jiang X, Lee CW. Protective immunity against influenza virus challenge by norovirus P particle-M2e and HA2-AtCYN vaccines in chickens. Vaccine. 2019 Oct 8;37(43):6454-6462. doi: 10.1016/j.vaccine.2019.08.082. Epub 2019 Sep 7. PubMed PMID: 31506195
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Dhakal S, Wang L, Antony L, Rank J, Bernardo P, Ghimire S, Bondra K, Siems C, Lakshmanappa YS, Renu S, Hogshead B, Krakowka S, Kauffman M, Scaria J, LeJeune JT, Yu Z, Renukaradhya GJ. Amish (Rural) vs. non-Amish (Urban) Infant Fecal Microbiotas Are Highly Diverse and Their Transplantation Lead to Differences in Mucosal Immune Maturation in a Humanized Germfree Piglet Model. Front Immunol. 2019 Jul 16;10:1509. doi: 10.3389/fimmu.2019.01509. eCollection 2019. PubMed PMID: 31379808; PubMed Central PMCID: PMC6648804
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Decline of transmissible gastroenteritis virus and its complex evolutionary relationship with porcine respiratory coronavirus in the United States. Chen F, Knutson TP, Rossow S, Saif LJ, Marthaler DG. Sci Rep. 2019 Mar 8;9(1):3953. doi: 10.1038/s41598-019-40564-z. PMID: 30850666
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Pathogenicity and immunogenicity of attenuated porcine epidemic diarrhea virus PC22A strain in conventional weaned pigs. Lin CM, Ghimire S, Hou Y, Boley P, Langel SN, Vlasova AN, Saif LJ, Wang Q. BMC Vet Res. 2019 Jan 11;15(1):26. doi: 10.1186/s12917-018-1756-x. PMID: 30634958
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Human Norovirus Histo-Blood Group Antigen (HBGA) Binding Sites Mediate the Virus Specific Interactions with Lettuce Carbohydrates. Esseili MA, Gao X, Boley P, Hou Y, Saif LJ, Brewer-Jensen P, Lindesmith LC, Baric RS, Atmar RL, Wang Q. Viruses. 2019 Sep 8;11(9). pii: E833. doi: 10.3390/v11090833. PMID: 31500340
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Updated classification of norovirus genogroups and genotypes. Chhabra P, de Graaf M, Parra GI, Chan MC, Green K, Martella V, Wang Q, White PA, Katayama K, Vennema H, Koopmans MPG, Vinj� J. J Gen Virol. 2019 Oct;100(10):1393-1406. doi: 10.1099/jgv.0.001318. PMID: 31483239
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: The enhanced replication of an S-intact PEDV during coinfection with an S1 NTD-del PEDV in piglets. Su Y, Hou Y, Wang Q. Vet Microbiol. 2019 Jan;228:202-212. doi: 10.1016/j.vetmic.2018.11.025. Epub 2018 Nov 27. PMID: 30593369
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Features of nutrition pattern of patients with small intestinal bacterial overgrowth resistant to therapy. Pilipenko VI, Isakov VA, Vlasova AV, Naidenova MA. Vopr Pitan. 2019;88(5):31-38. doi: 10.24411/0042-8833-2019-10051. Epub 2019 Sep 19. Russian. PMID: 31710785
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Advances in Diagnostic Approaches for Viral Etiologies of Diarrhea: From the Lab to the Field. Malik YS, Verma AK, Kumar N, Touil N, Karthik K, Tiwari R, Bora DP, Dhama K, Ghosh S, Hemida MG, Abdel-Moneim AS, B�nyai K, Vlasova AN, Kobayashi N, Singh RK. Front Microbiol. 2019 Sep 13;10:1957. doi: 10.3389/fmicb.2019.01957. eCollection 2019. Review. PMID: 31608017
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Epidemiology of Deltacoronaviruses (?-CoV) and Gammacoronaviruses (?-CoV) in Wild Birds in the United States. Paim FC, Bowman AS, Miller L, Feehan BJ, Marthaler D, Saif LJ, Vlasova AN. Viruses. 2019 Sep 26;11(10). pii: E897. doi: 10.3390/v11100897. PMID: 31561462
  • Type: Journal Articles Status: Awaiting Publication Year Published: 2019 Citation: Ghorbani A, Ngunjiri JM, Lee CW. Influenza A Virus Subpopulations and Their Implication in Pathogenesis and Vaccine Development. Annu Rev Anim Biosci. 2019. doi: 10.1146/annurev-animal-021419-083756. [Epub ahead of print]
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Ghorbani A, Ngunjiri JM, Xia M, Elaish M, Jang H, KC M, Abundo MC, Jiang X, Lee CW. Heterosubtypic protection by live attenuated and chimeric norovirus P-particle-M2e vaccines in chickens. Vaccine. 37(10):1356-1364. 2019.
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Deletion of both the Tyrosine-Based Endocytosis Signal and the Endoplasmic Reticulum Retrieval Signal in the Cytoplasmic Tail of Spike Protein Attenuates Porcine Epidemic Diarrhea Virus in Pigs. Hou Y, Meulia T, Gao X, Saif LJ, Wang Q. J Virol. 2019 Jan 4;93(2). pii: e01758-18. doi: 10.1128/JVI.01758-18. Print 2019 Jan 15. PMID: 30404797
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Emerging Highly Virulent Porcine Epidemic Diarrhea Virus: Molecular Mechanisms of Attenuation and Rational Design of Live Attenuated Vaccines. Hou Y, Wang Q. Int J Mol Sci. 2019 Nov 4;20(21). pii: E5478. doi: 10.3390/ijms20215478. Review. PMID: 31689903
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: GTPase-activating protein-binding protein 1 (G3BP1) plays an antiviral role against porcine epidemic diarrhea virus. Pandey K, Zhong S, Diel DG, Hou Y, Wang Q, Nelson E, Wang X. Vet Microbiol. 2019 Sep;236:108392. doi: 10.1016/j.vetmic.2019.108392. Epub 2019 Aug 19. PMID: 3150072
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: Madin-Darby canine kidney cell sialic acid receptor modulation induced by culture medium conditions: Implications for the isolation of influenza A virus. Nelson SW, Lorbach JN, Nolting JM, Stull JW, Jackwood DJ, Davis IC, Bowman AS. Influenza Other Respir Viruses. 2019 Nov;13(6):593-602. doi: 10.1111/irv.12671. Epub 2019 Aug 7. PMID: 31392833
  • Type: Journal Articles Status: Published Year Published: 2019 Citation: New introduction of a very virulent infectious bursal disease virus in New York, USA. Michel LO, Kimber ML, Jackwood DJ. Avian Pathol. 2019 Oct;48(5):486-491. doi: 10.1080/03079457.2019.1626975. Epub 2019 Jun 26. PMID: 31155926
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Amir Ghorbani, John M. Ngunjiri, Kara Taylor, Michael C. Abundo, and Chang-Won Lee. Systematic Development of Next-Generation NS1-Truncated Live Attenuated Influenza Vaccines by Targeting Viral Subpopulations with Enhanced Interferon-Inducing Capacity. OPTIONS X for the Control of Influenza, August 28 - September 1, 2019, Singapore.
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Replication of zoonotic genotype 3 hepatitis E virus (HEV) is enhanced by the ORF4 protein from human genotype 1 HEV. K. Yadav, P. Boley, Z. Fritts, and S. Kenney Presented at The Conference for Research Workers in Animal Diseases November 2019
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Qiuhong Wang. Norovirus in fresh produce. OHIO PRODUCE GROWERS & MARKETERS ASSOCIATION. January 16-17, 2019 - Embassy Suites (5100 Upper Metre Place Dublin, OH 43017).
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Qiuhong Wang. Study the molecular attenuation mechanisms of porcine epidemic diarrhea virus for rational design of effective vaccines. South Dakoda State University. Feb. 22, 2019
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Qiuhong Wang. Study the molecular attenuation mechanisms of porcine epidemic diarrhea virus for rational design of effective vaccines (in Chinese). Guangxi Veterinary Institute and Guangxi University. March 28, 2019
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Langel, S.N., Vlasova, A.N., Chimelo Paim, F., Alhamo, M.A., Lager, K., Saif, L.J. 2019. Vitamin A supplementation of PEDV infected gilts enhances IgA and lactogenic immune protection of nursing piglets. CRWAD, 2019, November 2-5, Chicago, IL.
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Tomoichiro Oka, Hiroyuki Saito, Takayuki Kobayashi, Tomoko Takahashi, Takashi Shimoike, Michiyo Kataoka, Qiuhong Wang, Linda J. Saif, Mamoru Noda, Hirotaka Takagi. Cell culture trials for human sapoviruses. The 7th International Calicivirus Conference in Sydney, Australia from October 13  October 16, 2019.
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Malak A. Esseili1, Xiang Gao, Patricia Boley, Yixuan Hou, Linda J. Saif, Paul Brewer-Jensen, Lisa Lindesmith, Ralph S. Baric, Robert L. Atmar, Mary K. Estes and Qiuhong Wang. Human norovirus HBGA binding pocket mediates the virus specific interactions with lettuce carbohydratesThe 7th International Calicivirus Conference in Sydney, Australia from October 13  October 16, 2019
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Amir Ghorbani, John M. Ngunjiri, Michael C. Abundo, Mohamed Elaish, Hana Ji, Kara Taylor, and Chang-Won Lee. Improvement of an NS1-truncated live attenuated influenza vaccine by selection of viral subpopulations with enhanced interferon inducing capability. The American Association of Avian Pathologists (AAAP) Annual meeting, August 2-5, 2019, Washington, D.C
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Amir Ghorbani, John M. Ngunjiri, Michael C. Abundo, Hana Ji, Kara Taylor, Mohamed Elaish, and Chang-Won Lee. Targeting Viral Subpopulations to Improve the Effectiveness of Live Attenuated Influenza Vaccine. 70th North Central Avian Disease Conference, March 12-14, 2019, Minneapolis, MN.
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Qiuhong Wang, Linda J Saif, Yixuan Hou, Chun-Ming Lin, Thavamathi Annamalai. Molecular attenuation mechanisms of porcine epidemic diarrhea virus (PEDV) in pigs. The 100th Conference for Research Workers in Animal Disease (CRWAD). Chicago, IL. Nov. 2-4, 2019
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Qiuhong Wang. Rational design of attenuated vaccines for porcine epidemic diarrhea virus. The 100th Conference for Research Workers in Animal Disease (CRWAD). Chicago, IL. Nov. 2-4, 2019
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: Mekonnen, Y.T., Deblais, L., Ghanem, M., Mohamed, Y., Chen, D., Singh, N., Ahyong, V., Kalantar, K., Yimer, G., Hassen, J.Y., Mohammed, A., McKune, S., Manary, M., Ordiz, I., Gebreyes, W., Havelaar, A., Rajashekara, G. Campylobacter species diversity in children and livestock in eastern Ethiopia. CRWAD 2019, November 2-5th, Chicago, IL
  • Type: Conference Papers and Presentations Status: Accepted Year Published: 2019 Citation: K. Yadav, P. Boley, Z. Fritts, and S. Kenney Replication of zoonotic genotype 3 hepatitis E virus (HEV) is enhanced by the ORF4 protein from human genotype 1 HEV. CRWAD 2019, November 2-5th, Chicago, IL