title: BVDV: a pestivirus inducing tolerance of the innate immune response.
abstract: Animals persistently infected (PI) with bovine viral diarrhea virus (BVDV) retain a strain-specific B- and T-cell immunotolerance. Pestiviral RNA triggers interferon (IFN) synthesis, and the viral RNase E(rns) inhibits IFN expression induced by extracellular viral RNA. In addition, N(pro) promotes the degradation of the transcription factor IRF-3, which effectively blocks IFN expression in BVDV-infected cells. As not all the potential target cells are infected in PI animals, these are 'chimeric' with respect to BVDV. This suggests that N(pro) and E(rns) are non-redundant IFN antagonists that act in infected and non-infected cells, respectively. Moreover, E(rns) may take a paradoxical function, both as virulence as well as "attenuation" factor: The former by preventing the activation of the innate and, consequently, of the adaptive immune system, the latter by minimizing the detrimental effects of systemic IFN production. Thus, BVDV maintains "self-tolerance" by avoiding the induction of IFN while itself being largely resistant to it without, however, interfering with the IFN action against unrelated viruses ('nonself'). This unique extension of 'self' to a virus suggests that the host's own RNases may have evolved as a guard against inadvertent activation of the innate immune system by host RNA, thus establishing a state of "innate tolerance".
authors.affiliation: Institute of Veterinary Virology, Vetsuisse Faculty University of Bern, Laenggass-Strasse 122, P.O. Box 8466, CH-3001 Bern, Switzerland. ernst.peterhans@vetsuisse.unibe.ch
authors.forename: Ernst
authors.initials: E
authors.lastname: Peterhans
authors.forename: Matthias
authors.initials: M
authors.lastname: Schweizer
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D002417:Cattle; D001908:Diarrhea Viruses, Bovine Viral / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D004722:Endoribonucleases / Q000276:immunology / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000276:immunology; D057131:Immune Evasion / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D050838:Interferon Regulatory Factor-3 / Q000276:immunology / Q000378:metabolism; D007372:Interferons / Q000276:immunology / Q000378:metabolism; D018448:Models, Immunological; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D050838:Interferon Regulatory Factor-3; C507353:Npro protein, bovine viral diarrhea virus; D014764:Viral Proteins; D007372:Interferons; D004722:Endoribonucleases; C022537:ribonuclease E