Progress 04/15/07 to 04/14/12
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
PI left the University of California Davis
Publications
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Progress 10/01/11 to 04/14/12
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
PD left UCD. Attempts to reach him have been unsuccessful.
Publications
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Progress 10/01/10 to 09/30/11
Outputs
Target Audience:
Nothing Reported
Changes/Problems:
Nothing Reported
What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
PD has left UCD. Attempts to reach him have been unsuccessful. Please remove from reporting cycle.
Publications
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Progress 01/01/10 to 09/30/10
Outputs
Target Audience:
Nothing Reported
Changes/Problems: Please remove from reporting cycle. This faculty member is no longer with UCD. What opportunities for training and professional development has the project provided?
Nothing Reported
How have the results been disseminated to communities of interest?
Nothing Reported
What do you plan to do during the next reporting period to accomplish the goals?
Nothing Reported
Impacts
What was accomplished under these goals?
This faculty member has left UCD. Attempts to reach him have been unsuccessful.
Publications
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Progress 01/01/09 to 12/31/09
Outputs
OUTPUTS: We have studied the gene expression patterns in chicken macrophages and lungs infected with low pathogenic avian influenza viruses, an H9N2 and an H6N2 viruses isolated in California, and found a unique pattern of proinflammatory cytokines and chemokine genes that were regulated upon infection; we have analyzed the effect of viral non-structural protein-1 (NS1) on the regulation of proinflammatory responses and apoptosis in infected chicken macrophages, using an NS1-deficient H9N2 virus prepared from reverse genetics approach; Furthermore, to understand the underlining mechanism regulating host responses in chickens, we examined the activation of mitogen-activated protein kineases (MAPK) upon infection and its effect on the regulation of host responses in avian influenza virus-infected chicken immune cells and demonstrated evidently how essential ERK and p38 are with regard to proinflammatory responses and how suppressive the actiated ERK is to the activation of infection-induced apoptosis, to the advantage of viral replication, in chicken immune cells. We extended our project to a comparative studies in chickens and ducks, in order to understand why these two species respond distinctly to avian influenza virus infection, using an H11N2 virus isolated from a duck and found that different immune responses were induced in their peripheral blood mononuclear cell cultures (PBMC), which may help explain differences in pathogenesis in chickens and ducks. PARTICIPANTS: INVESTIGATORs: Xing, Z.; Cardona, C. J. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
1. We have performed extensive studies on the gene expression and regulation in chicken immune cells and tissues infected with low pathogenic avian influenza viruses and exhibited the unique pattern of host responses in both proinflammatory and antiviral cytokines as well as infection-induced apoptotic response. These results are novel, not demonstrated in avian species in the past. 2. We were able to use mutant avian influenza virus, through reverse genetics approach, to analyze the impact of the viral gene, NS1, on the host responses in chicken immune cells. No comparative studies have been performed in avian species on the effect of viral NS1 on host apoptotic response. 3. We were the first to report that MAP kinases were activated in chicken immune cells infected with avian influenza virus, and how the activation of MAP kineases affect the host responses and pathogenesis in birds, which provides mechanistic insights on the regulation of the host responses and virus-host interaction in avian influenza virus-infected birds. No comparative studies have ever been performed in this field.
Publications
- Adams, S., Z. Xing, J.L. Li, and C.J. Cardona. 2009. Immune-related Gene Expression in Response to H11N9 Low Pathogenic Avian Influenza Virus Infection in Chicken and Pekin Duck Peripheral Blood Mononuclear Cells. Molecular Immunology, 46(8-9): 1744-9 (Epub ahead of print).
- Xing, Z., C.J. Cardona, S. Adams, Z.Q. Yang, J.L. Li, D. Perez and P.R. Woolcock. 2009. Differential Regulation of Antiviral and Proinflammatory Cytokines and Suppression of Fas-mediated Apoptosis by NS1 of H9N2 Avian Influenza Virus in Chicken Macrophages. Journal of General Virology, 90(5): 1109-18 (Epub ahead of print).
- Xing, Z., C.J. Cardona, J. Li, N. Dao, T. Tran, and J. Andrada. 2008. Modulation of Adaptive Immune Responses in Chickens by Low Pathogenicity Avian Influenza Virus H9N2. Journal of General Virology, 89(5): 88-99.
- Li, J., C.J. Cardona, Z. Xing and P. R. Woolcock. 2008. Genetic and phenotypic characterization of an unusual low pathogenic avian influenza virus. Archives of Virology, 153(10):1899-908. Cardona, C. J., Z. Xing, C. E. Sandrock, C. E. Davis. 2008. Avian influenza in birds and animals Comparative Immunology, Microbiology and Infectious Diseases, 32(4): 255-73.
- Xing, Z., C.J. Cardona, J.D. Anunciacion, and S.C. Adams. 2010. Roles of ERK MAPK in the regulation of Proinflammatory Cytokine and Fas-mediated Apoptosis in Avian Influenza Virus Infected Chicken Macrophages. Journal of General Virology, 91:343-51, 2010.
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Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: We have made the following progresses which are related to the goals and objectives since the project started: 1. Extensive Regulations of immune genes in chicken macrophages and lungs infected with influenza virus H9N2. Pro-inflammatory cytokines IL-1beta, IL-8, and chemokines K203, ah221 (CCL7), ah294, CCL3, CCL20, K60 (CXCL1) and CXCL14 were all upregulated from 1.3 to 26.7 fold in A/ph/CA/2373/98 (H9N2) virus infected Macrophages. However, cytokines IL-2, IL-6, IL-16, IL-17 as well as IL-4 receptor(IL-4R) and IL-21R were downregulated between 1.2 and 10.8 fold. We also found that interferon (IFN) and IFN-inducible genes were regulated differentially in A/ph/CA/2373/98 (H9N2) virus infected Macrophages. While 2'-5'-oligoadenylate synthetase (OAS)-like gene was upregulated at the 6th hour post infection up to 3.3 fold, Mx protein was downregulated marginally. Expression of IFN-inducible protein IP-30 was suppressed up to 2.4 fold but that of interferon-inducible 58 kDa
with tetratricopeptide repeats 5 (IFIT-5) was increased up to 20.1 fold in the early stage of infection (6 hrs post infection). IFN beta and gamma were both expressed at low levels in control Macrophages. While the IFN beta expression was increased up to 1.7 fold 12 hrs post infection, interferon gamma expression did not change. 2. Characterize the impact of immune modulation by LPAI viruses on host immune responses. We examined how the host adaptive immunity developed in both H6N2 and H9N2 virus-infected chickens. Swabs from 8 of 9 chickens infected with A/ch/CA/1772/02 (H6N2) had virus detectable by real time RT-PCR post inoculation through day 12. Within two weeks post infection, the Hemagglutination inhibition (HI) antibodies titers ranged from 1:20 to 1:160 and the seroconversion rate was 88.9% (8/9). In contrast, 8 of 9 chickens challenged with H9N2 shed viruses post inoculation through day 12 as detected by real-time RT-PCR, but all of the infected birds showed HI antibody
titers less than 1:20 and the seroconversion rate was 0% (0/9) two weeks post infection, indicating that the adaptive immune responses were suppreseed in H9N2 infected chickens. All challenged birds survived infection. Necropsy of the hens showed that the H9N2 virus infected hens had no grossly detectable lesions while some of the H6N2 virus infected hens had mild lesions in the respiratory tract. 3. Characterization of the viral genes that regulate host immune responses. We proposed to use reverse genetics apporach to study the roles of the viral genes that regulate host immune responses. We targeted NS1 gene of the H9N2 virus. At this stage we have cloned all eight segments of genomic cDNA into the vector pDP2000, transfected them in MDCK/293T cells and obtained rescued viruses which were infectious and could be passaged in cell cultures and embryonated eggs. We have also generated mutant NS1 gene and rescued the recombinant viruses which lacks in NS1. We will use the rescued
wild-type and NS1-mutant viruses for infection in both chicken macrophages and chickens. The regulated expression of immune genes and the regulation of the adaptive immune responses in infected chickens will be examined.
PARTICIPANTS: Xing, Z.: Department of Pathology, Microbiology & Immunology, School of Veterinary Medicine, UC Davis Cardona, C.J.: Department of Population Health & Reproduction, School of Veterinary Medicine, UC Davis Li, J.L.: Department of Population Health & Reproduction, School of Veterinary Medicine, UC Davis Dao, N.: Department of Population Health & Reproduction, School of Veterinary Medicine, UC Davis
TARGET AUDIENCES: Researchers and managers in poultry industry; Health professionals in veterinary and human infectious diseases;
PROJECT MODIFICATIONS: No major changes are taken at this stage.
Impacts
1. Regulated expression of immune genes in influenza virus-infected mammals have been extensively reported but our data were the first to report the immune responses in chicken macrophages responding to influenza virus infection. Our findings demonstrated that a correlation exists between the regulated gene expression in infected macrophages and the suppression of the antibody responses. This indicates that chicken macrophages could play a significant roles in both innate and adaptive immune responses in chickens infected with influenza viruses. 2. The virus strain, A/ph/CA/2373/98 (H9N2), caused extensive downregulation of immune genes and poor antibody responses in chickens. This fact showed the importance of the selection of candidate viral strains for live vaccine development. The viral strains, selected for live vaccine candidates, should have least suppressive impact on the the host immune responses.
Publications
- Zheng Xing1, Carol J. Cardona, Jinling Li, Nguyet Dao, Tu Tran, and Jason Andrada. 2008. Modulation of the Immune Responses in Chickens by Low Pathogenicity Avian Influenza Virus H9N2. Journal of General Virology, In press.
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