The rinderpest virus non-structural C protein blocks the induction of type 1 interferon

Abstract

The innate immune response, in particular the production of type 1 interferons, is an essential part of the mammalian host response to viral infection. We have previously shown that rinderpest virus, a morbillivirus closely related to the human pathogen measles virus, blocks the actions of type 1 and type 2 interferons. We show here that this virus can also block the induction of type 1 interferon. The viral non-structural C protein appears to be the active agent, since expressing this protein in cells makes them resistant to activation of the interferon-beta promoter while recombinant virus that does not express the C protein activates this promoter much more than virus expressing the C protein. In addition, differences in activation of the interferon-beta promoter by different strains of rinderpest virus are reflected in differing abilities of their respective C proteins to block activation of the promoter by dsRNA. The C protein blocks the activation of this promoter induced by either cytoplasmic dsRNA or by Newcastle disease virus (NDV) infection, as well as activation induced by overexpression of several elements of the signalling pathway, including mda-5, RIG-I and IRF-3. The RPV C protein also blocks transcription from promoters responsive individually to the three transcription factors that make up the interferon-beta promoter enhanceosome, although it does not appear to block the activation of IRF-3.