The viral RNase E(rns) prevents IFN type-I triggering by pestiviral single- and double-stranded RNAs.
Interferon (IFN) type-I is of utmost importance in the innate antiviral defence of eukaryotic cells. The cells express intra- and extracellular receptors that monitor their surroundings for the presence of viral genomes. Bovine viral diarrhoea virus (BVDV), a Pestivirus of the family Flaviviridae, is able to prevent IFN synthesis induced by poly(IC), a synthetic dsRNA. The evasion of innate immunity might be a decisive ability of BVDV to establish persistent infection in its host. We report that ds- as well as ssRNA fragments of viral origin are able to trigger IFN synthesis, and that the viral envelope glycoprotein E(rns), that is also secreted from infected cells, is able to inhibit IFN expression induced by these extracellular viral RNAs. The RNase activity of E(rns) is required for this inhibition, and E(rns) degrades ds- and ssRNA at neutral pH. In addition, cells infected with a cytopathogenic strain of BVDV contain more dsRNA than cells infected with the homologous non-cytopathogenic strain, and the intracellular viral RNA was able to excite the IFN system in a 5'-triphosphate-, i.e. RIG-I-, independent manner. Functionally, E(rns) might represent a decoy receptor that binds and enzymatically degrades viral RNA that otherwise might activate the IFN defence by binding to Toll-like receptors of uninfected cells. Thus, the pestiviral RNase efficiently manipulates the host's self-nonself discrimination to successfully establish and maintain persistence and immunotolerance.
Mätzener
Philippe
P
Institute of Veterinary Virology, University of Bern, Laenggass-Str. 122, P.O. Box 8466, CH-3001 Bern, Switzerland.
Magkouras
Ioannis
I
Rümenapf
Till
T
Peterhans
Ernst
E
Schweizer
Matthias
M
D000818:Animals; D001912:Bovine Virus Diarrhea-Mucosal Disease / Q000276:immunology / Q000821:virology; D002417:Cattle; D002460:Cell Line; D001908:Diarrhea Viruses, Bovine Viral / Q000276:immunology* / Q000378:metabolism; D004722:Endoribonucleases / Q000276:immunology / Q000378:metabolism*; D007370:Interferon Type I / Q000096:biosynthesis* / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D011070:Poly I-C / Q000276:immunology / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000276:immunology / Q000378:metabolism*; D012367:RNA, Viral / Q000276:immunology / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000276:immunology / Q000378:metabolism*
D007370:Interferon Type I; D008562:Membrane Glycoproteins; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D014759:Viral Envelope Proteins; D004722:Endoribonucleases; C022537:ribonuclease E; D011070:Poly I-C