Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom 73170, Thailand.
Viruses. 2021 Oct 15;13(10):2077. doi: 10.3390/v13102077.
Infections with viruses in the genus are a worldwide public health problem. These enveloped, positive sense single stranded RNA viruses use a small complement of only 10 encoded proteins and the RNA genome itself to remodel host cells to achieve conditions favoring viral replication. A consequence of the limited viral armamentarium is that each protein exerts multiple cellular effects, in addition to any direct role in viral replication. The viruses encode four non-structural (NS) small transmembrane proteins (NS2A, NS2B, NS4A and NS4B) which collectively remain rather poorly characterized. NS4A is a 16kDa membrane associated protein and recent studies have shown that this protein plays multiple roles, including in membrane remodeling, antagonism of the host cell interferon response, and in the induction of autophagy, in addition to playing a role in viral replication. Perhaps most importantly, NS4A has been implicated as playing a critical role in fetal developmental defects seen as a consequence of Zika virus infection during pregnancy. This review provides a comprehensive overview of the multiple roles of this small but pivotal protein in mediating the pathobiology of flaviviral infections.
属中的病毒感染是一个全球性的公共卫生问题。这些包膜的、正链单链 RNA 病毒仅使用一小部分 10 个编码蛋白和 RNA 基因组本身来重塑宿主细胞，以达到有利于病毒复制的条件。病毒武器库有限的结果是，每种蛋白除了在病毒复制中直接发挥作用外，还对细胞产生多种影响。这些病毒编码了四个非结构（NS）小跨膜蛋白（NS2A、NS2B、NS4A 和 NS4B），它们的综合特征仍然相当差。NS4A 是一种 16kDa 的膜相关蛋白，最近的研究表明，该蛋白发挥多种作用，包括在膜重塑、拮抗宿主细胞干扰素反应以及诱导自噬方面，除了在病毒复制中发挥作用外。也许最重要的是，NS4A 被认为在寨卡病毒感染引起的胎儿发育缺陷中起着关键作用。本综述全面概述了该小但关键蛋白在介导黄病毒感染的病理生物学中的多种作用。
