What can pestiviral endonucleases teach us about innate immunotolerance?

Lussi, Carmela; Schweizer, Matthias (2016). What can pestiviral endonucleases teach us about innate immunotolerance? Cytokine & growth factor reviews, 29, pp. 53-62. Elsevier 10.1016/j.cytogfr.2016.03.003

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Pestiviruses including bovine viral diarrhea virus (BVDV), border disease virus (BDV) and classical swine fever virus (CSFV), occur worldwide and are important pathogens of livestock. A large part of their success can be attributed to the induction of central immunotolerance including B- and T-cells upon fetal infection leading to the generation of persistently infected (PI) animals. In the past few years, it became evident that evasion of innate immunity is a central element to induce and maintain persistent infection. Hence, the viral non-structural protease N(pro) heads the transcription factor IRF-3 for proteasomal degradation, whereas an extracellularly secreted, soluble form of the envelope glycoprotein E(rns) degrades immunostimulatory viral single- and double-stranded RNA, which makes this RNase unique among viral endoribonucleases. We propose that these pestiviral interferon (IFN) antagonists maintain a state of innate immunotolerance mainly pertaining its viral nucleic acids, in contrast to the well-established immunotolerance of the adaptive immune system, which is mainly targeted at proteins. In particular, the unique extension of 'self' to include the viral genome by degrading immunostimulatory viral RNA by E(rns) is reminiscent of various host nucleases that are important to prevent inappropriate IFN activation by the host's own nucleic acids in autoimmune diseases such as Aicardi-Goutières syndrome or systemic lupus erythematosus. This mechanism of "innate tolerance" might thus provide a new facet to the role of extracellular RNases in the sustained prevention of the body's own immunostimulatory RNA to act as a danger-associated molecular pattern that is relevant across various species.

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)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Lussi, Carmela and Schweizer, Matthias

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 630 Agriculture

ISSN:

1879-0305

Publisher:

Elsevier

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

24 Jul 2017 15:35

Last Modified:

24 Jul 2017 15:35

Publisher DOI:

10.1016/j.cytogfr.2016.03.003

PubMed ID:

27021825

Uncontrolled Keywords:

Bovine viral diarrhea virus (BVDV); IFN antagonist; Innate immunotolerance; Persistent infection; Self-nonself discrimination; Viral endoribonuclease

BORIS DOI:

10.7892/boris.96157

URI:

https://boris.unibe.ch/id/eprint/96157

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