Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication.
Impacts of p97 on Proteome Changes in Human Cells during Coronaviral Replication.
复制标题
DOI：
10.3390/cells10112953
复制
发表时间：
2021-10-29
期刊：
影响因子：
6
通讯作者：
Chou TF
中科院分区：
文献类型：
--
作者：
Cheng KW;Li S;Wang F;Ruiz-Lopez NM;Houerbi N;Chou TF
人类冠状病毒（HCoV）与其他病毒类似，依靠宿主细胞机制进行复制和传播。p97/VCP atp酶与多种可能有利于HCoV复制的途径相关。在这项研究中，我们评估了p97在HCoV-229E或HCoV-OC43感染后在人肺细胞系H1299中的作用和相关的宿主反应。小分子抑制剂抑制p97功能显示抗病毒活性，特别是在病毒生命周期的早期阶段，在病毒脱壳和病毒RNA复制期间。重要的是，p97活性抑制保护人类细胞免受hcov诱导的细胞病变效应。p97基因的敲除也会抑制感染细胞中的病毒产生。无偏定量蛋白质组学分析显示，HCoV-OC43感染导致病毒复制过程中细胞衰老和DNA修复中富集的蛋白质组学变化。进一步分析感染细胞与对照和p97 shRNA之间的蛋白变化，确定HCoV-229E和HCoV-OC43感染的细胞周期途径。总之，我们的数据表明必需宿主蛋白p97在支持HCoV复制中的作用，表明p97是治疗HCoV感染的治疗靶点。
Human coronavirus (HCoV) similar to other viruses rely on host cell machinery for both replication and to spread. The p97/VCP ATPase is associated with diverse pathways that may favor HCoV replication. In this study, we assessed the role of p97 and associated host responses in human lung cell line H1299 after HCoV-229E or HCoV-OC43 infection. Inhibition of p97 function by small molecule inhibitors shows antiviral activity, particularly at early stages of the virus life cycle, during virus uncoating and viral RNA replication. Importantly, p97 activity inhibition protects human cells against HCoV-induced cytopathic effects. The p97 knockdown also inhibits viral production in infected cells. Unbiased quantitative proteomics analyses reveal that HCoV-OC43 infection resulted in proteome changes enriched in cellular senescence and DNA repair during virus replication. Further analysis of protein changes between infected cells with control and p97 shRNA identifies cell cycle pathways for both HCoV-229E and HCoV-OC43 infection. Together, our data indicate a role for the essential host protein p97 in supporting HCoV replication, suggesting that p97 is a therapeutic target to treat HCoV infection.
登录
查看更多内容
影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
影响因子：
5
作者：
Phongphaew W;Kobayashi S;Sasaki M;Carr M;Hall WW;Orba Y;Sawa H
通讯作者：
Sawa H
影响因子：
3.7
作者：
Friedman N;Jacob-Hirsch J;Drori Y;Eran E;Kol N;Nayshool O;Mendelson E;Rechavi G;Mandelboim M
通讯作者：
Mandelboim M
影响因子：
16.6
作者：
Kokic G;Hillen HS;Tegunov D;Dienemann C;Seitz F;Schmitzova J;Farnung L;Siewert A;Höbartner C;Cramer P
通讯作者：
Cramer P
影响因子：
8.8
作者：
Panda D;Rose PP;Hanna SL;Gold B;Hopkins KC;Lyde RB;Marks MS;Cherry S
通讯作者：
Cherry S