Laboratory of Virology, Wageningen University, Wageningen, The Netherlands.
J Virol. 2013 Sep;87(18):10394-400. doi: 10.1128/JVI.00884-13. Epub 2013 Jul 17.
Alphavirus nonstructural protein 2 (nsP2) has pivotal roles in viral RNA replication, host cell shutoff, and inhibition of antiviral responses. Mutations that individually rendered other alphaviruses noncytopathic were introduced into chikungunya virus nsP2. Results show that (i) nsP2 mutation P718S only in combination with KR649AA or adaptive mutation D711G allowed noncytopathic replicon RNA replication, (ii) prohibiting nsP2 nuclear localization abrogates inhibition of antiviral interferon-induced JAK-STAT signaling, and (iii) nsP2 independently affects RNA replication, cytopathicity, and JAK-STAT signaling.
甲病毒非结构蛋白 2（nsP2）在病毒 RNA 复制、宿主细胞关闭和抑制抗病毒反应方面发挥着关键作用。将单独使其他甲病毒无细胞病变的突变引入到基孔肯雅病毒 nsP2 中。结果表明：（i）仅 P718S 突变与 KR649AA 或适应性突变 D711G 相结合才能允许无细胞病变复制子 RNA 复制；（ii）阻止 nsP2 核定位会破坏抗病毒干扰素诱导的 JAK-STAT 信号转导的抑制；（iii）nsP2 独立影响 RNA 复制、细胞病变和 JAK-STAT 信号转导。
