Race against Time between the Virus and Host: Actin-Assisted Rapid Biogenesis of Replication Organelles is Used by TBSV to Limit the Recruitment of Cellular Restriction Factors
Race against Time between the Virus and Host: Actin-Assisted Rapid Biogenesis of Replication Organelles is Used by TBSV to Limit the Recruitment of Cellular Restriction Factors
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DOI：
10.1128/jvi.00168-21
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发表时间：
2022-05-31
影响因子：
5.4
通讯作者：
Nagy，Peter D.
中科院分区：
文献类型：
--
作者：
Molho，Melissa;Zhu，Shifeng;Nagy，Peter D.
正链RNA病毒在宿主因子的帮助下构建大型病毒复制细胞器（VROs）。先前对番茄丛矮病毒（TBSV）的研究表明，p33复制蛋白通过分离肌动蛋白解聚因子cofilin来破坏肌动蛋白细胞骨架，从而减少肌动蛋白丝的分解并稳定肌动蛋白丝。然后，TBSV利用稳定的肌动蛋白丝作为“运输公路”，将原宿主因子运送到具有保护性的VROs中。在这项工作中，我们发现细胞内在限制因子（cirf）也使用肌动蛋白网络到达VROs并抑制病毒复制。通过表达elegionellaravk蛋白酶破坏肌动蛋白丝抑制植物cirf的募集，包括cypa样的Roc1和Roc2亲环蛋白，以及抗病毒ddx17样的RH30 DEAD盒解旋酶进入VROs。相反，具有稳定肌动蛋白丝的温度敏感型肌动蛋白和cofilin突变型酵母降低了病毒复制酶制剂中共纯化cirf的水平，包括亲环蛋白Cpr1、CypA、cyp40样Cpr7、cochaperones Sgt2、hop样Sti1和RH30解旋酶。前病毒因子和抗病毒宿主因子的募集依赖于肌动蛋白网络上的VROs，这表明TBSV与其宿主之间存在一种利用肌动蛋白网络的竞争，并最终在感染过程中占据上风。我们认为，在高度易感植物中，tombusvirus有效地破坏肌动蛋白网络，将原宿主因子快速传递到VROs中，并最终通过赢得招募竞赛和压倒细胞防御来克服宿主限制因子。正链RNA病毒的ereplication受到宿主成分招募的影响，这些宿主成分在病毒入侵感染细胞期间提供前病毒或抗病毒功能。这些宿主因子进入代表病毒RNA复制位点的病毒复制细胞器（VROs），取决于细胞肌动蛋白网络。利用TBSV，我们发现了病毒和宿主之间的竞争，其中肌动蛋白网络是核心参与者。我们发现，在易感植物中，熊状病毒利用肌动蛋白网络将原宿主因子快速传递到VROs中，并最终克服宿主限制因子。总之，这项工作表明肌动蛋白网络在决定植物病毒感染的结果中起着重要作用。
Positive-strand RNA viruses build large viral replication organelles (VROs) with the help of coopted host factors. Previous works on tomato bushy stunt virus (TBSV) showed that the p33 replication protein subverts the actin cytoskeleton by sequestering the actin depolymerization factor, cofilin, to reduce actin filament disassembly and stabilize the actin filaments. Then, TBSV utilizes the stable actin filaments as “trafficking highways” to deliver proviral host factors into the protective VROs. In this work, we show that the cellular intrinsic restriction factors (CIRFs) also use the actin network to reach VROs and inhibit viral replication. Disruption of the actin filaments by expression of theLegionellaRavK protease inhibited the recruitment of plant CIRFs, including the CypA-like Roc1 and Roc2 cyclophilins, and the antiviral DDX17-like RH30 DEAD box helicase into VROs. Conversely, temperature-sensitive actin and cofilin mutant yeasts with stabilized actin filaments reduced the levels of copurified CIRFs, including cyclophilins Cpr1, CypA, Cyp40-like Cpr7, cochaperones Sgt2, the Hop-like Sti1, and the RH30 helicase in viral replicase preparations. Dependence of the recruitment of both proviral and antiviral host factors into VROs on the actin network suggests that there is a race going on between TBSV and its host to exploit the actin network and ultimately to gain the upper hand during infection. We propose that, in the highly susceptible plants, tombusviruses efficiently subvert the actin network for rapid delivery of proviral host factors into VROs and ultimately overcome host restriction factors via winning the recruitment race and overwhelming cellular defenses.IMPORTANCEReplication of positive-strand RNA viruses is affected by the recruitment of host components, which provide either proviral or antiviral functions during virus invasion of infected cells. The delivery of these host factors into the viral replication organelles (VROs), which represent the sites of viral RNA replication, depends on the cellular actin network. Using TBSV, we uncover a race between the virus and its host with the actin network as the central player. We find that in susceptible plants, tombusviruses exploit the actin network for rapid delivery of proviral host factors into VROs and ultimately overcome host restriction factors. In summary, this work demonstrates that the actin network plays a major role in determining the outcome of viral infections in plants.