Pestiviral E(rns) blocks TLR-3-dependent IFN synthesis by LL37 complexed RNA

Zürcher, Christoph Martin; Sauter, Kay Sara; Schweizer, Matthias (2014). Pestiviral E(rns) blocks TLR-3-dependent IFN synthesis by LL37 complexed RNA. Veterinary microbiology, 174(3-4), pp. 399-408. Elsevier 10.1016/j.vetmic.2014.09.028

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The ribonuclease activity of the soluble glycoprotein E(rns) of pestiviruses represents a unique mechanism to circumvent the host's innate immune system by blocking interferon type-I synthesis in response to extracellularly added single- (ss) and double-stranded (ds) RNA. However, the reason why pestiviruses encode a ribonuclease in addition to the abundant serum RNases remained elusive. Here, we show that the 5' UTR and NS5B regions of various strains of the RNA genome of the pestivirus bovine viral diarrhea virus (BVDV) are resistant to serum RNases and are potent TLR-3 agonists. Inhibitory activity of E(rns) was restricted to cleavable RNA products, and did not extend to the synthetic TLR-7/8 agonist R-848. RNA complexed with the antimicrobial peptide LL37 was protected from degradation by E(rns)in vitro but was fully inhibited by E(rns) in its ability to induce IFN in cell cultures, suggesting that the viral protein is mainly active in cleaving RNA in an intracellular compartment. We propose that secreted E(rns) represents a potent IFN antagonist, which degrades viral RNA that is resistant to the ubiquitous host RNases in the extracellular space. Thus, the viral RNase prevents its own pathogen-associated molecular pattern (PAMP) to inadvertently activate the IFN response that might break innate immunotolerance required for persistent pestivirus infections.

Item Type:

Journal Article (Original 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:

Zürcher, Christoph Martin; Sauter, Kay Sara and Schweizer, Matthias

Subjects:

600 Technology > 630 Agriculture

ISSN:

0378-1135

Publisher:

Elsevier

Language:

English

Submitter:

Barbara Gautschi-Steffen

Date Deposited:

14 Apr 2015 15:27

Last Modified:

15 Oct 2015 10:52

Publisher DOI:

10.1016/j.vetmic.2014.09.028

PubMed ID:

25457366

Uncontrolled Keywords:

Bovine viral diarrhea virus (BVDV); Interferon (IFN); Viral endoribonuclease; Secondary structure; Human cathelicidin LL37; TLR-3

BORIS DOI:

10.7892/boris.66705

URI:

https://boris.unibe.ch/id/eprint/66705

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