HSP70 Copurifies with Zika Virus Particles
HSP70 Copurifies with Zika Virus Particles
复制标题
DOI：
10.1016/j.virol.2018.07.009
复制
发表时间：
2018-09-01
期刊：
影响因子：
3.7
通讯作者：
French, Samuel W.
中科院分区：
文献类型：
--
作者：
Khachatoorian, Ronik;Cohn, Whitaker;French, Samuel W.
寨卡病毒（ZIKV）已被确定为婴儿神经系统疾病和格林巴利综合症的病因，目前尚未批准任何治疗方法或疫苗。在这项研究中，我们试图识别与 ZIKV 颗粒相互作用的潜在宿主蛋白，以更好地了解病毒感染性。通过密度梯度离心和随后的尺寸排阻色谱（SEC）纯化病毒颗粒。质谱分析显示病毒包膜蛋白和 HSP70 仅在一个 SEC 级分中共迁移。在任何其他 SEC 级分中均未发现这些蛋白质。然后我们进行了中和测定，发现将病毒颗粒与 HSP70 抗体一起孵育确实显着降低了病毒感染性，而 HSC70 抗体却没有。用重组 HSP70 预孵育细胞也降低了病毒感染性。 HSP70 的敲低和抑制也显着减少了病毒的产生。这些结果表明 HSP70 参与了 ZIKV 的发病机制，并将 HSP70 确定为针对 ZIKV 感染的潜在宿主治疗靶点。
Zika virus (ZIKV) has been identified as a cause of neurologic diseases in infants and Guillain-Barre Syndrome, and currently, no therapeutics or vaccines are approved. In this study, we sought to identify potential host proteins interacting with ZIKV particles to gain better insights into viral infectivity. Viral particles were purified through density-gradient centrifugation and subsequently, size-exclusion chromatography (SEC). Mass spectrometric analyses revealed viral envelope protein and HSP70 to comigrate in only one SEC fraction. Neither of these proteins were found in any other SEC fractions. We then performed neutralization assays and found that incubating viral particles with antibody against HSP70 indeed significantly reduced viral infectivity, while HSC70 antibody did not. Preincubating cells with recombinant HSP70 also decreased viral infectivity. Knockdown and inhibition of HSP70 also significantly diminished viral production. These results implicate HSP70 in the pathogenesis of ZIKV and identify HSP70 as a potential host therapeutic target against ZIKV infection.