Septin 2 与登革热病毒复制复合物蛋白相互作用，并参与蚊细胞中的病毒复制。

Septin 2 interacts with dengue virus replication complex proteins and participates in virus replication in mosquito cells.

机构信息

Department of Infectomics and Molecular Pathogenesis, Center for Research and Advanced Studies (CINVESTAV-IPN), Mexico City, 07360, Mexico.

Laboratorio Central de Epidemiología, Centro Médico Nacional La Raza, Instituto Mexicano del Seguro Social, Mexico City, 02990, Mexico.

出版信息

Virology. 2022 May;570:67-80. doi: 10.1016/j.virol.2022.03.007. Epub 2022 Mar 27.

DOI:10.1016/j.virol.2022.03.007

PMID:35390695

Abstract

Septins are a family of GTP-binding proteins identified in insects and mammals. Septins are components of the cytoskeleton and participate in cytokinesis, chromosomal segregation, intracellular vesicular traffic, and response to pathogens. Human septin 6 was identified as necessary for hepatitis C virus replication. Information about host factors necessary for flavivirus replication in mosquitoes is scarce. Thus, the role of septins in the replicative cycle of dengue virus in Aedes spp. derived cells was investigated. Through bioinformatic analysis, sequences of septin-like proteins were identified. Infected mosquito cells showed increased expression of Sep2. Colocalization analysis, proximity ligation and immunoprecipitation assays indicated that Sep2 interacts with proteins E, NS3 and NS5, but not NS1. Immunoelectron microscopy evidenced the presence of AalSep2 in replicative complexes. Finally, silencing of Sep2 expression resulted in a significant decrease in virus progeny, indicating that Sep2 is a host factor participating in dengue virus replication in mosquito cells.

摘要

Septins 是一类在昆虫和哺乳动物中被发现的 GTP 结合蛋白。它们是细胞骨架的组成部分，参与细胞分裂、染色体分离、细胞内囊泡运输以及对病原体的反应。人类 septin 6 被确定为丙型肝炎病毒复制所必需的。关于蚊子中黄病毒复制所需的宿主因子的信息很少。因此，研究了在登革热病毒在按蚊衍生细胞中的复制周期中 septin 的作用。通过生物信息学分析，鉴定了 septin 样蛋白的序列。感染蚊子的细胞中 Sep2 的表达增加。共定位分析、邻近连接和免疫沉淀实验表明，Sep2 与蛋白 E、NS3 和 NS5 相互作用，但与 NS1 不相互作用。免疫电子显微镜证据表明 AalSep2 存在于复制复合物中。最后，Sep2 表达的沉默导致病毒产物显著减少，表明 Sep2 是参与蚊子细胞中登革热病毒复制的宿主因子。