RNase-dependent inhibition of extracellular, but not intracellular, dsRNA-induced interferon synthesis by Erns of pestiviruses.
Recombinant pestivirus envelope glycoprotein E(rns) has been shown to interfere with dsRNA-induced interferon (IFN-alpha/beta) synthesis. This study demonstrated that authentic, enzymically active E(rns) produced in mammalian cells prevented a dsRNA-induced IFN response when present in the supernatant of bovine cells. Strikingly, IFN synthesis of cells expressing E(rns) was eliminated after extracellular addition, but not transfection, of dsRNA. Importantly, the same applied to cells infected with bovine viral diarrhea virus (BVDV) expressing E(rns) but lacking the N-terminal protease N(pro). Free E(rns) concentrations circulating in the blood of animals persistently infected with BVDV were determined to be approximately 50 ng ml(-1), i.e. at a similar order of magnitude as that displaying an effect on dsRNA-induced IFN expression in vitro. Whilst N(pro) blocks interferon regulatory factor-3-dependent IFN induction in infected cells, E(rns) may prevent constant IFN induction in uninfected cells by dsRNA that could originate from pestivirus-infected cells. This probably contributes to the survival of persistently BVDV-infected animals and maintains viral persistence in the host population.
Magkouras
Ioannis
I
Institute of Veterinary Virology, University of Bern, CH-3001 Bern, Switzerland.
Mätzener
Philippe
P
Institute of Veterinary Virology, University of Bern, CH-3001 Bern, Switzerland.
Rümenapf
Till
T
Institute of Virology (FB Veterinärmedizin), Justus-Liebig-University Giessen, D-35392 Giessen, Germany.
Peterhans
Ernst
E
Institute of Veterinary Virology, University of Bern, CH-3001 Bern, Switzerland.
Schweizer
Matthias
M
Institute of Veterinary Virology, University of Bern, CH-3001 Bern, Switzerland.
D000818:Animals; D002417:Cattle; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D001908:Diarrhea Viruses, Bovine Viral / Q000378:metabolism / Q000472:pathogenicity*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D007372:Interferons / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D012330:RNA, Double-Stranded / Q000235:genetics / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism
D012330:RNA, Double-Stranded; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; D007372:Interferons; D004722:Endoribonucleases; D012260:Ribonucleases