Sendai virus C protein inhibits lipopolysaccharide-induced nitric oxide production through impairing interferon-β signaling

• Sendai virus (SeV) inhibits endotoxin (LPS)-induced nitric oxide (NO) production.
• C gene-knockout 4C(−) SeV does not inhibit LPS-induced NO production.
• C protein inhibits LPS-induced iNOS and NO expression.
• C protein but not the mutant one inhibits LPS-induced ISRE reporter activity.
• SeV C protein might be a therapeutic tool for endotoxin-induced tissue injury.

The effect of Sendai virus (SeV) C protein on lipopolysaccharide (LPS)-induced nitric oxide (NO) production was examined using RAW 264.7 macrophage cells. Infection of SeV inhibited LPS-induced NO production via downregulating the expression of an inducible NO synthase protein (iNOS). On the other hand, C gene-knockout 4C(−) SeV inhibited neither NO production nor iNOS expression. Wild type and 4C(−) SeV did not affect LPS-induced production of tumor necrosis factor-α and interleukin-6, and further LPS-induced activation of nuclear factor (NF)-κB and mitogen-activated protein kinases. Although wild type and 4C(−) SeV did not inhibit LPS-induced interferon (IFN)-β production, wild type SeV but not 4C(−) SeV inhibited the activation of STAT1/2 in the IFN-β signaling. SeV C protein inhibited LPS-induced iNOS expression and NO production. C protein inhibited the promotor activation of IFN-β and IFN-sensitive response element (ISRE) in response to LPS whereas the C mutant protein CF170S, which lacks the ability to block the STAT activation, did not inhibit it. Taken together, SeV C protein was suggested to inhibit LPS-induced NO production through impairing IFN-β signaling.