Institut Pasteur, Virus and Immunity Unit, CNRS-UMR3569, Paris, France
Institut Pasteur, Virus and Immunity Unit, CNRS-UMR3569, Paris, France.
J Virol. 2019 Nov 13;93(23). doi: 10.1128/JVI.01047-19. Print 2019 Dec 1.
The endoplasmic reticulum (ER) is the site for Zika virus (ZIKV) replication and is central to the cytopathic effects observed in infected cells. ZIKV induces the formation of ER-derived large cytoplasmic vacuoles followed by "implosive" cell death. Little is known about the nature of the ER factors that regulate flavivirus replication. Atlastins (ATL1, -2, and -3) are dynamin-related GTPases that control the structure and the dynamics of the ER membrane. We show here that ZIKV replication is significantly decreased in the absence of ATL proteins. The appearance of infected cells is delayed, the levels of intracellular viral proteins and released virus are reduced, and the cytopathic effects are strongly impaired. We further show that ATL3 is recruited to viral replication sites and interacts with the nonstructural viral proteins NS2A and NS2B3. Thus, proteins that shape and maintain the ER tubular network ensure efficient ZIKV replication. Zika virus (ZIKV) is an emerging virus associated with Guillain-Barré syndrome, and fetal microcephaly as well as other neurological complications. There is no vaccine or specific antiviral treatment against ZIKV. We found that endoplasmic reticulum (ER)-shaping atlastin proteins (ATL1, -2, and -3), which induce ER membrane fusion, facilitate ZIKV replication. We show that ATL3 is recruited to the viral replication site and colocalize with the viral proteins NS2A and NS2B3. The results provide insights into host factors used by ZIKV to enhance its replication.
内质网（ER）是寨卡病毒（ZIKV）复制的场所，也是感染细胞中观察到的细胞病变效应的核心。ZIKV 诱导 ER 衍生的大细胞质空泡的形成，随后是“内爆”细胞死亡。关于调节黄病毒复制的 ER 因子的性质知之甚少。Atlastins（ATL1、-2 和 -3）是与 dynamin 相关的 GTP 酶，可控制 ER 膜的结构和动力学。我们在这里表明，在没有 ATL 蛋白的情况下，ZIKV 复制显著减少。感染细胞的出现被延迟，细胞内病毒蛋白和释放的病毒水平降低，细胞病变效应受到强烈损害。我们进一步表明，ATL3 被募集到病毒复制位点，并与非结构病毒蛋白 NS2A 和 NS2B3 相互作用。因此，塑造和维持 ER 管状网络的蛋白质确保了有效的 ZIKV 复制。寨卡病毒（ZIKV）是一种新兴病毒，与格林-巴利综合征、胎儿小头畸形以及其他神经并发症有关。目前还没有针对 ZIKV 的疫苗或特定的抗病毒治疗方法。我们发现，内质网（ER）成形蛋白 atlastin（ATL1、-2 和 -3）促进 ZIKV 复制，ATL1、-2 和 -3 诱导 ER 膜融合。我们表明，ATL3 被募集到病毒复制位点，并与病毒蛋白 NS2A 和 NS2B3 共定位。这些结果提供了宿主因子的深入了解，ZIKV 利用这些因子来增强其复制。
