BVDV: a pestivirus inducing tolerance of the innate immune response

Peterhans, Ernst; Schweizer, Matthias (2013). BVDV: a pestivirus inducing tolerance of the innate immune response. Biologicals, 41(1), pp. 39-51. Elsevier 10.1016/j.biologicals.2012.07.006

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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".

Item Type:

Journal Article (Review Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Peterhans, Ernst and Schweizer, Matthias

Subjects:

600 Technology > 630 Agriculture

ISSN:

1045-1056

Publisher:

Elsevier

Language:

English

Submitter:

Susanne Portner

Date Deposited:

28 Jul 2014 13:52

Last Modified:

14 Oct 2015 11:37

Publisher DOI:

10.1016/j.biologicals.2012.07.006

PubMed ID:

22871358

Uncontrolled Keywords:

Co-evolution, Innate immunotolerance, Interferon, Pestivirus, Self-nonself discrimination, Viral RNase

URI:

https://boris.unibe.ch/id/eprint/45949

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