Progress 09/01/03 to 08/31/05
Outputs
Porcine reproductive and respiratory syndrome virus (PRRSv) causes a prolonged viremia and persistent infection in lymphoid tissues of pigs. Since polyclonal activation of B cells and hypergammaglobulinemia are hallmarks of many persistent viral infections and are reported in neonatal PRRSv infection, we hypothesized that nonspecific polyclonal humoral and B cell responses would be present in blood and lymphoid tissues of pigs infected with PRRSv. Total and protein (KLH)-specific Ig levels were determined in serum pigs over time. Total serum Ig also was determined biochemically. Total, KLH-specific, and PRRSv protein-specific antibody secreting cells (ASC) were enumerated by ELISPOT in primary and secondary lymphoid tissues. The level of serum anti-KLH Ig was unaffected by PRRSV infection over a 60 day period. Total serum Ig in infected pigs increased by about 50% compared to uninfected pigs. The same relative difference also occurred in pigs infected with porcine
circovirus-2, consistent with specific antibody responses to viral infection. Absence of hypergammaglobulinemia was paralleled by absence of polyclonal B cell activation; the frequency of IgG-ASC and anti-KLH ASC were the same in spleen, tonsil, bone marrow and draining lymph nodes of PRRSv-infected and uninfected pigs over a period of 120 days. We conclude that this persistent viral infection does not elicit a nonspecific activation of B cells.
Impacts
A better understanding of the mechanisms of resistance to PRRSV will assist in the development of better methods of protection of pigs against PRRSV infection. Consequences of better protection would include improvement in the livelihoods of swine farmers and allied industries, enhanced rural life resulting from more vigorous local communities, expanded export markets, and better provision to American consumers of a safe and nutritious food supply.
Publications
- Olin, M.R., L. Batista, Z. Xiao, S.A. Dee, M.P. Murtaugh, C.C. Pijoan, and T.W. Molitor. 2005. ?? lymphocyte response to porcine reproductive and respiratory syndrome virus. Viral Immunol. 18:490-499.
- Batista, L., C. Pijoan, S. Dee, M. Olin, T. Molitor, H.S. Joo, Z. Xiao, and M. Murtaugh. 2004. Virological and immunological features of homologous and heterologous protection to porcine reproductive and respiratory syndrome virus in a large population of gilts. Can. J. Vet. Res. 68:267-273.
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Progress 01/01/04 to 12/31/04
Outputs
Weak and transient cellular immune response and an inappropriate humoral response in PRRSV infection indicate impaired immunity, which could be related to impaired dendritic cell function. Therefore, we examined the interaction of PRRSV with macrophage-matured dendritic cells (DCs). Differentiation of DCs from macrophages did not change the expression of sialoadhesin, the receptor for PRRSV. We found that dendritic cells are readily infected by PRRSV and virus titers peaked about 48 hours after infection. PRRSV infection of DC is cytolytic, as in macrophages. PRRSV infection did not alter cell surface expression of MHC class I, MHC class II, or CD80/86. However, infected DC demonstrated impaired function in an allogeneic mixed lymphocyte reaction. Furthermore, blockade of sialoadhesin by monoclonal antibody did not affect PRRSV infection of bone marrow-derived DCs and alveolar macrophage-derived DCs except at very high concentrations, which suggests PRRSV may infect
DCs by a route not involving sialoadhesin. Therefore, viral infection of DCs may be a new mechanism for PRRSV to partially escape immune system, and cause long time viral persistence, and weak immunity. We also have investigated the growth of PRRSV in macrophages from various tissues. PRRSV grew to significantly higher titers in vitro in monocytes and macrophages from spleen and bone marrow than in alveolar macrophages, suggesting that the viral receptor is not the essential determinant of viral infectivity in different tissues. Levels of sialoadhesin were much higher on alveolar macrophages of young pigs than of adult pigs. Also, its expression was identical on all macrophages in young pigs, whereas there were two subpopulations, low and high, in adults. After PRRSV infection a third population of sialoadhesin-negative cells appeared in the lung, but not in macrophages from lymphoid tissues. This suggests that a reduction of permissive cells occurs in the lung after PRRSV infection
and might be important in the elimination of PRRSV from pigs. Residual PRRSV in alveolar macrophages isolated from acutely and persistently infected pigs did not grow in macrophages cultured in vitro, whereas exogenous virus grew to the same high titer in cells isolated from infected and non-infected pig lungs. These findings indicate that the resolution of PRRSV persistence may be due to the decline of permissive macrophages in infected animals and that viral permissiveness is determined by processes that are not fully reproduced in cell culture.
Impacts
A better understanding of the mechanisms of resistance to PRRSV will assist in the development of better methods of protection of pigs against PRRSV infection. Consequences of better protection would include improvement in the livelihoods of swine farmers and allied industries, enhanced rural life resulting from more vigorous local communities, expanded export markets, and better provision to American consumers of a safe and nutritious food supply.
Publications
- Xiao, Z., L. Batista, S. Dee, P. Halbur and M.P. Murtaugh. 2004. The level of virus-specific T-cell and macrophage recruitment in porcine reproductive and respiratory syndrome virus infection in pigs is independent of the virus load. J. Virol. 78:5923-5933.
- Johnson, W., M. Roof, E. Vaughn, J. Christopher-Hennings, C.R. Johnson, and M.P. Murtaugh. 2004. Pathogenic and immunological responses to porcine reproductive and respiratory syndrome virus (PRRSV) are related to viral load in acute infection. Vet. Immunol. Immunopathol. 102:233-247.
- Murtaugh, M.P. 2004. PRRS immunology: what are we missing? Proc. Ann. Meet. Amer. Assoc. Swine Vet. pp. 359-367.
- Murtaugh, M.P. and R.R.R. Rowland. 2004. Preface. Vet. Immunol. Immunopathol. 102:105.
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Progress 01/01/03 to 12/31/03
Outputs
Adaptive immunity, consisting of antibodies and T lymphocytes, is required to clear infectious agents from animals and to establish long-term protection. Strong responses result in rapid clearance and sterilizing immunity. Infections that resolve slowly, with persistence of pathogens in tissues even after clearance from the circulation, indicate that the adaptive immune response is not completely effective. Characterization of adaptive immune responses to food animal pathogens is essential to the development of better vaccines and treatments. In this project on which work is just commencing, we will characterize changes in adaptive immune responses in pigs during clearance of a disseminated persistent infection caused by porcine reproductive and respiratory syndrome virus (PRRSV) and identify factors important for stimulation of the immune system. We hypothesize that the immune response to acute PRRSV infection in swine is dominated initially by antibodies that clear
circulating virus from blood. Subsequent persistent infection in tissues is resolved only after development of T cell immunity. We will test the hypotheses by determining (a) the relationship between PRRSV-specific immune responses and elimination of virus from blood and lymphoid tissues, (b) the relationship between viral mutation and elimination of virus from infected pigs, and (c) the effect of anti-viral immune stimulation on the duration of acute and persistent infection ending with virus elimination. A novel contribution of the proposed research is the characterization of differential immune responses, both humoral and T cell-mediated, to nonstructural and structural viral proteins. We expect that the results of this study will provide basic knowledge regarding protective immunity in the pig, an important livestock species. The findings will aid in the development of better methods for disease protection and may identify new immunological correlates of protective immunity with
diagnostic and clinical applications.
Impacts
We expect that the results of this study will provide basic knowledge regarding protective immunity in the pig, an important livestock species. The findings will aid in the development of better methods for disease protection and may identify new immunological correlates of protective immunity with diagnostic and clinical applications. PRRS is a devastating disease the directly affects the swine industry, including family farmers, veterinarians, rural communities, and service businesses. The work has the potential to affect all people that participate in the swine industry and benefit from eating pork.
Publications
- No publications reported this period
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