The matrix protein of Newcastle disease virus inhibits inflammatory response through IRAK4/TRAF6/TAK1/NF-?B signaling pathway

The matrix (M) protein of several cytoplasmic RNA viruses has been reported to be an NF-kappa B pathway antagonist. However, the function and mechanism of NDV M protein antagonizing NF-kappa B activation remain largely un-known. In this study, we found that the expression levels of IRAK4, TRAF6, TAK1, and RELA/p65 were obviously reduced late in NDV infection. In addition, the cytoplasmic M protein rather than other viral proteins decreased the expression of these proteins in a dose-dependent manner. Further indepth analysis showed that the N -ter-minal 180 amino acids of M protein were not only responsible for the reduced expression of these proteins, but also responsible for the inhibition of NF-kappa B activation and nuclear translocation of RELA/p65, as well as the production of inflammatory cytokines. Moreover, small interference RNA-mediated knockdown of IRAK4 or overexpression of IRAK4 markedly enhanced or reduced NDV replication by decreasing or increasing inflam-matory cytokines production through the IRAK4/TRAF6/TAK1/NF-kappa B signaling pathway. Strangely, there were no interactions detected between NDV M protein and IRAK4, TRAF6, TAK1 or RELA/p65. Our findings described here contribute to a better understanding of the innate immune antagonism function of M protein and the molecular mechanism underlying the replication and pathogenesis of NDV.