Japanese Encephalitis Virus Core Protein Inhibits Stress Granule Formation through an Interaction with Caprin-1 and Facilitates Viral Propagation
Japanese Encephalitis Virus Core Protein Inhibits Stress Granule Formation through an Interaction with Caprin-1 and Facilitates Viral Propagation
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DOI：
10.1128/jvi.02186-12
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发表时间：
2013-01-01
影响因子：
5.4
通讯作者：
Matsuura, Yoshiharu
中科院分区：
文献类型：
--
作者：
Katoh, Hiroshi;Okamoto, Toru;Matsuura, Yoshiharu
应激颗粒(SGS)是由环境应激刺激(包括病毒感染)诱导的停滞的翻译预起始复合体组成的细胞质焦点。由于病毒的传播完全依赖于宿主的翻译机制，许多病毒已经进化成避开SGS或coopt SG组分的诱导。在本研究中，我们发现乙脑病毒(JEV)核心蛋白的表达抑制了SG的形成。通过亲和捕获质谱分析，确定Caprin-1是核心蛋白的结合伙伴。丙氨酸扫描突变显示，JEV核心蛋白α-螺旋上的Lys(97)和Arg(98)在与Caprin-1的相互作用中起着关键作用。在感染变异JEV的细胞中，核心蛋白中的丙氨酸取代了Lys(97)和Arg(98)，抑制了SG的形成，并损害了病毒的繁殖。此外，突变的乙型脑炎病毒对小鼠的毒力减弱。这些结果表明，JEV核心蛋白通过与Caprin-1相互作用来抑制SG的形成，从而绕过翻译关闭，并促进病毒在体外和体内的繁殖。
Stress granules (SGs) are cytoplasmic foci composed of stalled translation preinitiation complexes induced by environmental stress stimuli, including viral infection. Since viral propagation completely depends on the host translational machinery, many viruses have evolved to circumvent the induction of SGs or co-opt SG components. In this study, we found that expression of Japanese encephalitis virus (JEV) core protein inhibits SG formation. Caprin-1 was identified as a binding partner of the core protein by an affinity capture mass spectrometry analysis. Alanine scanning mutagenesis revealed that Lys(97) and Arg(98) in the alpha-helix of the JEV core protein play a crucial role in the interaction with Caprin-1. In cells infected with a mutant JEV in which Lys(97) and Arg(98) were replaced with alanines in the core protein, the inhibition of SG formation was abrogated, and viral propagation was impaired. Furthermore, the mutant JEV exhibited attenuated virulence in mice. These results suggest that the JEV core protein circumvents translational shutoff by inhibiting SG formation through an interaction with Caprin-1 and facilitates viral propagation in vitro and in vivo.