COUNTERMEASURES TO CONTROL VIRAL DISEASES OF CATTLE
Location: Ruminant Diseases and Immunology Research Unit
Title: Characterization of viral replication and the immune response in bison peripheral blood mononuclear cells following in vitro bovine viral diarrhea virus infection
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: September 12, 2011
Publication Date: November 17, 2011
Citation: McGill, J.L., Schaut, R.G., Neill, J.D., Olsen, S.C., Ridpath, J.F., Sacco, R.E. 2011. Characterization of viral replication and the immune response in bison peripheral blood mononuclear cells following in vitro bovine viral diarrhea virus infection [abstract]. In: Proceedings of the U.S. Bovine Viral Diarrhea Virus Symposium, November 17-18, 2011, San Diego, California. p. 59.
Bovine viral diarrhea virus (BVDV) is a Pestivirus of the family Flaviviridae that has significant negative economic impact on beef and dairy production worldwide. In recent years, the North American bison industry has grown considerably with increases in the numbers of both wild and private herds. With this growth has come heightened concern about their susceptibility to and potential to become reservoirs of bovine respiratory pathogens. There is evidence in the literature demonstrating bison are susceptible to BVDV infection, and seroconversion prevalence has been shown to be as high as 55% in some studies. However, the overall knowledge of BVDV infection in bison and the mechanisms of disease therein, remain lacking. To this end, the overall objective of this study is to characterize the differences in permissivity and the resulting immune response of bison and bovine cells to BVDV infection, and to elucidate the mechanisms underlying differences in clinical disease and infection between bison and cattle. Peripheral blood samples were collected from clinically healthy, adult male and female bison or adult, healthy female Holstein-Friesian heifers. Peripheral blood mononuclear cells (PBMC) were then mock infected or infected in vitro with 0.5 MOI of BVDV type-2 strain 296C or 296NC, isogenic cytopathic and non-cytopathic strains, respectively; BVDV type-2 strain 1373, a highly virulent strain; or BVDV type-2 strain 28508-5, a low virulence strain. Viral replication and cytokine mRNA expression was compared between bovine and bison PBMC at various time points post infection (p.i.). A separate group of PBMC were infected with the various BVDV strains for 48 hours, then restimulated with PMA and Ionomycin for 6 or 24 hours, and analyzed for cytokine mRNA expression following secondary stimulation. Bison PBMC are susceptible to infection by BVDV type 2 viruses, with preliminary results suggesting that viral titers reach levels comparable to those observed in infected bovine PBMC. Infection by BVDV results in increased production of the inflammatory cytokines IL-1beta, TNFalpha, IL-8, IL-6, and IL-12p40 by both bison and bovine PBMC as early as 6 hours p.i. We observed a significant reduction in inflammatory cytokine production, in particular, IL-1beta and TNFalpha, following secondary PMA/Ionomycin stimulation of BVDV-infected bison PBMC compared to mock infected controls. These results are similar to the immunosuppression to secondary stimuli that is observed in bovine PBMC following in vitro BVDV infection. Preliminary results suggest there are no significant differences between the virus strains in their ability to induce inflammatory cytokine production in bison PBMC, or their ability to suppress responses to secondary stimuli. PBMC from bison are permissive to BVDV infection and appear similar to bovine PBMC in their immune response to in vitro infection. The immunosuppression to secondary stimuli that is observed following BVDV infection of bovine PBMC is also apparent in bison PBMC, suggesting that BVDV may not only cause primary disease in bison, but may also predispose to secondary infections, similar to the pathogenesis observed in BVDV infected cattle.