Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Virology. 2012 Mar 1;424(1):45-55. doi: 10.1016/j.virol.2011.12.011. Epub 2012 Jan 9.
Measles virus (MV) belongs to the genus Morbillivirus of the family Paramyxoviridae. A number of paramyxoviruses inhibit host interferon (IFN) signaling pathways in host immune systems by various mechanisms. Inhibition mechanisms have been described for many paramyxoviruses. Although there are inconsistencies among previous reports concerning MV, it appears that P/V/C proteins interfere with the pathways. In this study, we confirmed the effects of MV P gene products of a wild MV strain on IFN pathways and examined that of other viral proteins on it. Interestingly, we found that N protein acts as an IFN-α/β and γ-antagonist as strong as P gene products. We further investigated the mechanisms of MV-N inhibition, and revealed that MV-N blocks the nuclear import of activated STAT without preventing STAT and Jak activation or STAT degradation, and that the nuclear translocation of MV-N is important for the inhibition. The inhibitory effect of the N protein was observed as a common feature of other morbilliviruses. The results presented in this report suggest that N protein of MV as well as P/V/C proteins is involved in the inhibition of host IFN signaling pathways.
麻疹病毒(MV)属于副粘病毒科副粘病毒属。许多副粘病毒通过各种机制抑制宿主免疫系统中的干扰素(IFN)信号通路。已经描述了许多副粘病毒的抑制机制。尽管以前关于 MV 的报告存在不一致之处,但似乎 P/V/C 蛋白会干扰这些通路。在这项研究中,我们证实了野生 MV 株的 MV P 基因产物对 IFN 通路的影响,并研究了其他病毒蛋白对其的影响。有趣的是,我们发现 N 蛋白作为 IFN-α/β 和 γ 拮抗剂的作用与 P 基因产物一样强。我们进一步研究了 MV-N 抑制的机制,揭示 MV-N 阻止激活的 STAT 的核输入,而不阻止 STAT 和 Jak 的激活或 STAT 的降解,并且 MV-N 的核易位对于抑制是重要的。N 蛋白的抑制作用被观察为其他麻疹病毒的共同特征。本报告中的结果表明,MV 的 N 蛋白以及 P/V/C 蛋白均参与宿主 IFN 信号通路的抑制。