C and V proteins of Sendai virus target signaling pathways leading to IRF-3 activation for the negative regulation of interferon-beta production.

We here report a molecular basis for downregulation of interferon (IFN)-beta production by V and C proteins of Sendai virus (SeV). The infection of HeLa cells with SeV poorly induced IFN-beta even if the expression of C/C' was disrupted. In contrast, when the expression of C/C'/Y1/Y2 or V/W was disrupted, SeV infection strongly induced IFN-beta production and significantly activated the interferon regulatory factor (IRF)-3 pathway.

The C-terminal half-fragment of the Sendai virus C protein prevents the gamma-activated factor from binding to a gamma-activated sequence site.

Sendai virus C protein associates with the signal transducer and activator of transcription (STAT) 1 and inhibits the interferon (IFN) response. We report a molecular basis for the anti-IFN-gamma mechanism of Sendai virus. The C-terminal half-fragment of the C protein (D1) retains both the STAT1-binding and the anti-IFN-gamma abilities comparable to those of the full-size C.

The STAT2 activation process is a crucial target of Sendai virus C protein for the blockade of alpha interferon signaling.

Sendai virus (SeV) C protein functions as an interferon (IFN) antagonist and renders cells unresponsive to both alpha/beta IFN (IFN-alpha/beta) and IFN-gamma. We have recently found the physical association of the C protein with signal transducer and activator of transcription 1 (STAT1) in infected cells. However, involvement of the C-STAT1 interaction in the blockade of IFN signaling has remained unclear.

Paramyxovirus strategies for evading the interferon response.

Two genera, the Respirovirus (Sendai virus (SeV) and human parainfluenza virus (hPIV3) and the Rubulavirus (simian virus (SV) 5, SV41, mumps virus and hPIV2), of the three in the subfamily Paramyxovirinae inhibit interferon (IFN) signalling to circumvent the IFN response. The viral protein responsible for the inhibition is the C protein for respirovirus SeV and the V protein for the rubulaviruses, both of which are multifunctional accessory proteins expressed from the P gene. SeV suppresses IFN-stimulated tyrosine phosphorylation of signal transducers and activators of transcription (STATs) at an early phase of infection and further inhibits the downstream signalling without degrading any of the signalling components in most cell lines.

Paramyxovirus accessory proteins as interferon antagonists.

A new role of the Paramyxovirus accessory proteins has been uncovered. The P gene of the subfamily Paramyxovirinae encodes accessory proteins including the V and/or C protein by means of pseudotemplated nucleotide addition (RNA editing) or by overlapping open reading frame. The Respirovirus (Sendai virus and human parainfluenza virus (hPIV)3) and Rubulavirus (simian virus (SV)5, SV41, mumps virus and hPIV2) circumvent the interferon (IFN) response by inhibiting IFN signaling.