Pawlotsky J M, Germanidis G
Department of Bacteriology and Virology and INSERM U99, Hôpital Henri Mondor, Université Paris XII, Créteil, France.
J Viral Hepat. 1999 Sep;6(5):343-56. doi: 10.1046/j.1365-2893.1999.00185.x.
The non-structural (NS)5A protein of hepatitis C virus (HCV) is cleaved, after translation, by the NS3-encoded zinc-dependent serine proteinase, from the NS4B protein upstream and the NS5B protein downstream. The released, mature NS5A protein is a 56 000 MW phosphoprotein (p56), which also exists within infected cells in a hyperphosphorylated form (p58). The NS5A gene has a quasispecies distribution, meaning that various NS5A sequences co-exist, in various proportions, in infected individuals. HCV NS5A appears to be located in cytoplasmic membranes surrounding the nucleus. Its precise functions are not known. HCV non-structural proteins, including NS5A, form a large multiprotein replication complex, which probably directs the replication of the HCV genome. HCV NS5A lacking the 146 N-terminal amino acids is a potent transcriptional activator in vitro. NS5A can also bind to single-strand RNA-dependent protein kinase (PKR) and inhibit its antiviral function. An 'interferon (IFN) sensitivity-determining region' has recently been postulated in the NS5A protein central region in hepatitis C virus (HCV) genotype 1b, but strongly conflicting evidence has been published. In fact, there would seem to be no such region in the NS5A protein, even though NS5A plays an important and complex role in HCV resistance to IFN. Structure-function studies are required to identify precisely how NS5A and IFN interact.
丙型肝炎病毒（HCV）的非结构（NS）5A蛋白在翻译后，被NS3编码的锌依赖性丝氨酸蛋白酶从上游的NS4B蛋白和下游的NS5B蛋白处切割下来。释放出的成熟NS5A蛋白是一种分子量为56000的磷蛋白（p56），它在受感染细胞内也以高度磷酸化的形式（p58）存在。NS5A基因具有准种分布，这意味着在受感染个体中，各种NS5A序列以不同比例共存。HCV NS5A似乎位于细胞核周围的细胞质膜中。其确切功能尚不清楚。包括NS5A在内的HCV非结构蛋白形成一个大型多蛋白复制复合体，该复合体可能指导HCV基因组的复制。缺少146个N端氨基酸的HCV NS5A在体外是一种有效的转录激活因子。NS5A还可以与单链RNA依赖性蛋白激酶（PKR）结合并抑制其抗病毒功能。最近在丙型肝炎病毒（HCV）1b基因型的NS5A蛋白中央区域假定了一个“干扰素（IFN）敏感性决定区域”，但已发表了相互矛盾的有力证据。事实上，NS5A蛋白中似乎不存在这样一个区域，尽管NS5A在HCV对IFN的抗性中起着重要而复杂的作用。需要进行结构功能研究来精确确定NS5A与IFN是如何相互作用的。
