Knockout of the Sendai virus C gene eliminates the viral ability to prevent the interferon‐α/β‐mediated responses

Abstract

Sendai virus (SeV) renders cells unresponsive to interferon (IFN)-K K. To identify viral factors involved in this process, we examined whether recombinant SeVs, which could not express V protein, subsets of C proteins (C, CP P, Y1 and Y2) or any of four C proteins, retained the capability of impeding IFN-K K-mediated responses. Among these viruses, only the 4C knockout virus completely lost the ability to suppress the induction of IFN-K K-stimulated gene products and the subsequent establishment of an anti-viral state. These findings reveal crucial roles of the SeV C proteins in blocking IFN-K K-mediated responses.z 1999 Federation of European Biochemical Societies.

The STAT2 Activation Process Is a Crucial Target of Sendai Virus C Protein for the Blockade of Alpha Interferon Signaling

“…Longer C protein-specific degradation of STAT1 in NIH 3T3 mouse MEF cells, however, appears to be a special case. Because the expression of the C protein did not cause STAT1 degradation in most cell lines, including four human cell lines (HeLa, U118, 2fTGH, and HEC1B) and one mouse cell line (BF) (12,18,23,24,42,49). During the progress of our research, two related studies were published.…”

“…The V proteins of other rubulaviruses, including human parainfluenza virus type 2, mumps virus, and simian virus 41 inhibit IFN signaling likewise by inducing a decrease in the STAT1 or STAT2 level (8,25,30,31,34,35,47,49). In contrast, the respirovirus Sendai virus (SeV), which possesses both V and C ORFs, has evolved functions of the C protein instead of the V protein so as to block IFN signaling (12,18). The SeV C ORF produces a nested set of four C proteins, CЈ, C, Y1, and Y2, which are referred to collectively as the C proteins (5,14).…”

“…In addition to the C protein, the shorter forms, Y1 and Y2, have the ability to inhibit IFN signaling (11,22). The C protein, however, does not lead to degradation of any component on the signaling pathway in most cell types (12,18,24,42,49) except for NIH 3T3 mouse embryo fibroblast (MEF) cells (10,11). The purpose of the present study was to better understand how the SeV C protein inhibits IFN-␣ signaling without degrading cellular proteins on the signaling pathway.…”

The Ebola virus VP35 protein functions as a type I IFN antagonist

“…Subsequently, the V protein of SV5 was shown to target STAT1 for proteasome-mediated degradation, preventing signaling from both type I and type II IFN receptors (13,14). Also, the Sendai virus C proteins were found to block types I and II IFN signaling and to counteract the establishment of an antiviral state (15)(16)(17). Recently, measles virus infection has been shown to block induction of type I IFN production (18).…”

Involvement of the Zinc-Binding Capacity of Sendai Virus V Protein in Viral Pathogenesis

“…In contrast to the well-characterized P protein, little is known about the functions of the C and V proteins. The C proteins have been shown to be indispensable for efficient virus multiplication and pathogenicity (18), and they have also been shown to block interferon-mediated antivirus responses (11,12). The SeV V protein is reportedly able to suppress virus genome RNA replication in vitro with a defective interfering minigenome model (5).…”