SGTA-Dependent Regulation of Hsc70 Promotes Cytosol Entry of Simian Virus 40 from the Endoplasmic Reticulum
SGTA-Dependent Regulation of Hsc70 Promotes Cytosol Entry of Simian Virus 40 from the Endoplasmic Reticulum
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DOI：
10.1128/jvi.00232-17
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发表时间：
2017-06-01
影响因子：
5.4
通讯作者：
Tsai, Billy
中科院分区：
文献类型：
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作者：
Dupzyk, Allison;Williams, Jeffrey M.;Tsai, Billy
非包膜病毒的膜穿透仍然是个谜。在非包膜多瘤病毒类人猿病毒40 （SV40）的情况下，病毒穿透内质网（ER）膜到达细胞质，然后运输到细胞核引起感染。我们之前证明了细胞质Hsc70-SGTA-Hsp105复合物粘附在内质网膜上，Hsp105和SGTA促进从内质网中提取SV40并将病毒转运到细胞质中。我们现在发现Hsc70也通过SGTA调控的步骤将SV40从内质网喷射到细胞质中。虽然SGTA的n端结构域介导同二聚化和募集细胞接头，在SV40的内质网到胞质转运过程中是必不可少的，但在SV40进入过程中，该结构域似乎发挥了意想不到的内质网膜转运功能。因此，我们的研究确定了Hsc70在Hsc70-SGTA- hsp105复合体中促进SV40 er -胞质膜渗透的关键功能，并揭示了SGTA在控制这一步骤中的作用。重要性：非包膜病毒如何穿越生物膜而引起感染仍然是个谜。一个令人费解的步骤是宿主细胞质成分是否被增选以将病毒颗粒运输到细胞质中。在非包膜多瘤病毒SV40的ERto-cytosol膜运输过程中，一个决定性的感染步骤，由Hsc70-SGTA-Hsp105组成的胞质复合物先前被证明与内质网膜相关。SGTA和Hsp105已被证明能从内质网中提取SV40并将病毒转运到细胞质中。我们在这里展示了Hsc70在SV40 ER-to-cytosol渗透中的关键作用，并揭示了SGTA如何控制Hsc70来影响这一过程。
Membrane penetration by nonenveloped viruses remains enigmatic. In the case of the nonenveloped polyomavirus simian virus 40 (SV40), the virus penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol and then traffics to the nucleus to cause infection. We previously demonstrated that the cytosolic Hsc70-SGTA-Hsp105 complex is tethered to the ER membrane, where Hsp105 and SGTA facilitate the extraction of SV40 from the ER and transport of the virus into the cytosol. We now find that Hsc70 also ejects SV40 from the ER into the cytosol in a step regulated by SGTA. Although SGTA's N-terminal domain, which mediates homodimerization and recruits cellular adaptors, is dispensable during ER-to-cytosol transport of SV40, this domain appears to exert an unexpected post-ER membrane translocation function during SV40 entry. Our study thus establishes a critical function of Hsc70 within the Hsc70-SGTA-Hsp105 complex in promoting SV40 ER-to-cytosol membrane penetration and unveils a role of SGTA in controlling this step.IMPORTANCE How a nonenveloped virus transports across a biological membrane to cause infection remains mysterious. One enigmatic step is whether host cytosolic components are co-opted to transport the viral particle into the cytosol. During ERto-cytosol membrane transport of the nonenveloped polyomavirus SV40, a decisive infection step, a cytosolic complex composed of Hsc70-SGTA-Hsp105 was previously shown to associate with the ER membrane. SGTA and Hsp105 have been shown to extract SV40 from the ER and transport the virus into the cytosol. We demonstrate here a critical role of Hsc70 in SV40 ER-to-cytosol penetration and reveal how SGTA controls Hsc70 to impact this process.