Sendai Virus C Proteins Counteract the Interferon-Mediated Induction of an Antiviral State

Abstract

We have studied the relationship between the Sendai virus (SeV) C proteins (a nested set of four proteins initiated at different start codons) and the interferon (IFN)-mediated antiviral response in IFN-competent cells in culture. SeV strains containing wild-type or various mutant C proteins were examined for their ability (i) to induce an antiviral state (i.e., to prevent the growth of vesicular stomatitis virus [VSV] following a period of SeV infection), (ii) to induce the elevation of Stat1 protein levels, and (iii) to prevent IFN added concomitant with the SeV infection from inducing an antiviral state. We find that expression of the wild-type C gene and, specifically, the AUG114-initiated C protein prevents the establishment of an antiviral state: i.e., cells infected with wild-type SeV exhibited little or no increase in Stat1 levels and were permissive for VSV replication, even in the presence of exogenous IFN. In contrast, in cells infected with SeV lacking the AUG114-initiated C protein or containing a single amino acid substitution in the C protein, the level of Stat1 increased and VSV replication was inhibited. The prevention of the cellular IFN-mediated antiviral response appears to be a key determinant of SeV pathogenicity.

Hendra and Nipah viruses: different and dangerous

“…Inhibition of dsRNA signalling. In the henipaviruses, dsRNA signalling is inhibited not only by the accessory V protein, as observed for rubulaviruses and respiroviruses [93][94][95]100,101 , but surprisingly also by the accessory W protein (FIG. 3).…”

“…4). SeV and hPIV3 inhibit tyrosine phosphorylation of STAT1, STAT2 or TYK2, a process that requires the accessory C protein 95,100,101,116 . Several anti-IFN-signalling strategies have been proposed for MeV, all of which leave STAT proteins intact but prevent their translocation to the nucleus 117 .…”

Interplay between Innate Immunity and Negative-Strand RNA Viruses: towards a Rational Model

“…C proteins from RPV (30), MeV (262), and SeV (82,89,270) inhibit the activation of the IFN-␤ gene mediated by RIG-I stimulated by an artificial RNA agonist (30,262,270) or by viral infection. This effect is moderate and variable according to the virus strain (30,77) and is also observed in cells devoid of the IFN/IFNAR amplification loop (30).…”

Reverse Genetics of Measles Virus and Resulting Multivalent Recombinant Vaccines: Applications of Recombinant Measles Viruses

“…This view is supported by later studies with Sendai virus, showing that ablation of C-type proteins leads to heavily compromised viruses, since Sendai C-type proteins interfere with interferon responses. In addition, these proteins are involved in transcription/replication (Delenda et al 1998;Garcin et al 1999Garcin et al , 2000Garcin et al , 2001Garcin et al , 2002. The MV C-mutant replicated poorly in human peripheral blood cells (PBMCs) (Escoffier et al 1999) as well as in human thymus/liver implants in SCID mice (Valsamakis et al 1998), suggesting a role of C protein also in the transcription/ replication of MV.…”