Efficient sensing of infected cells in absence of virus particles by plasmacytoid dendritic is blocked by the viral ribonuclease Erns (P6114)

Abstract

Abstract Plasmacytoid dendritic cells (pDC) have been shown to efficiently sense HCV- or HIV-infected cells. Here we demonstrate for classical swine fever virus, a member of the Flaviviridae, that this process is much more efficient in terms of interferon-alpha induction when compared to direct stimulation by virus particles. By employment of virus replicon particles which can replicate but not form de novo virions, we exclude a transfer of virus from the donor cell to the pDC. pDC activation by infected cells to pDC was mediated by a contact-dependent RNA transfer to TLR7, requiring intact cytoskeleton, lipid rafts, but not involving membrane vesicles such as exosomes. We further demonstrate that a unique viral protein with ribonuclease activity, the Erns protein of pestiviruses, efficiently prevented this process. This required intact ribonuclease function in intracellular compartments. The present study underlines the importance of pDC activation by infected cells and identifies a novel pathway of virus escaping the interferon system. This pathway of activation could be of particular importance for viruses which are cell-associated and cause persistent infection. Considering that Erns is required for pestiviruses to establish persistent infection of foetuses after transplacental virus transmission resulting in the development of immunotolerant animals, this report also points on a possible role of pDC in preventing immunotolerance after viral infection of foetuses.