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RNase-dependent inhibition of extracellular, but not intracellular, dsRNA-induced interferon synthesis by E^rns of pestiviruses

Ioannis Magkouras^1,

Philippe Mätzener^1,

¹ Institute of Veterinary Virology, University of Bern, CH-3001 Bern, Switzerland
² Institute of Virology (FB Veterinärmedizin), Justus-Liebig-University Giessen, D-35392 Giessen, Germany

Correspondence
Matthias Schweizer
matthias.schweizer{at}ivv.unibe.ch

Recombinant pestivirus envelope glycoprotein E^rns has been shown to interfere with dsRNA-induced interferon (IFN-/β) 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.

These authors contributed equally to this work.

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