Hepatitis C virus nonstructural region 5A protein is a potent transcriptional activator.
Hepatitis C virus nonstructural region 5A protein is a potent transcriptional activator.
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DOI：
10.1007/978-4-431-68488-6_4
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发表时间：
1997-11
影响因子：
5.4
通讯作者：
Naoya Kato;K. Lan;S. Ono‐Nita;Y. Shiratori;Masao Omata
中科院分区：
文献类型：
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作者：
Naoya Kato;K. Lan;S. Ono‐Nita;Y. Shiratori;Masao Omata
丙型肝炎病毒（HCV）是一种基因组大小约为10千碱基的正链RNA病毒，与黄病毒科的黄病毒和鼠疫病毒有远亲关系[1,2]。采用反转录法和聚合酶链反应（RT-PCR）检测非甲、非乙型肝炎患者血清中的HCV RNA。HCV RNA RT-PCR分析显示，慢性肝病抗HCV阳性患者多数为HCV携带者[3]。HCV基因组包含一个大的开放阅读框，编码3010-3033个氨基酸的多蛋白前体，在基因组的5 ‘和3 ’端有一个未翻译区（UTR）。HCV基因组的推定组织包括5 ' UTR， 3个结构蛋白，7个非结构（NS）蛋白和3 ‘ UTR，顺序从5 ’端[4]开始。NS5A蛋白是一种丝氨酸磷酸化蛋白，具有两种亚型p56和p58 （p56的过度磷酸化形式）[5]。在临床上，HCV-lb NS5A基因突变与慢性活动性肝炎患者对干扰素-α的反应密切相关[6,7]。最近，NS5A蛋白被证明可以结合干扰素诱导的抗病毒蛋白PKR（双链rna依赖蛋白激酶），并抑制其激酶活性[8]。然而，NS5A蛋白的功能尚不完全清楚。我们发现NS5A蛋白具有类似核定位的信号序列，并且定位于核质周膜部分，因此它可能具有一些与转录或翻译[9]相关的功能。
Hepatitis C virus (HCV) is a positive-stranded RNA virus of genomic size of approximately 10 kilobases which is distantly related to the flaviviruses and the pestiviruses of the flavivirus family [1,2]. HCV RNA is detected in the serum of patients with non-A, non-B hepatitis using the assay method of reverse transcription followed by the polymerase chain reaction (RT-PCR). RT-PCR analysis of HCV RNA shows that the majority of anti-HCV-positive patients with chronic liver disease are HCV carriers [3]. The HCV genome contains a large open reading frame encoding a polyprotein precursor of 3010–3033 amino acids and an untranslated region (UTR) at the 5′ and 3′ ends of the genome. The putative organization of the HCV genome includes the 5′ UTR, 3 structural proteins, 7 nonstructural (NS) proteins, and the 3′ UTR, in order from the 5′ end [4]. One of the NS proteins, NS5A protein, is a serine phosphoprotein with two isoforms, p56 and p58 (the hyperphosphorylated form of p56) [5]. Clinically, a close association was demonstrated between mutations in the NS5A gene of HCV-lb and the response to interferon-α in patients with chronic active hepatitis [6,7]. Recently, the NS5A protein was shown to bind interferon-induced antiviral protein, PKR (double-stranded RNA-dependent protein kinase), and inhibit its kinase activity [8]. However, the function of the NS5A protein is still not fully understood. The NS5A protein was found to possess a nuclear localization-like signal sequence and to be localized in the nuclear periplasmic membrane fraction, so it seems that it may have some function related to transcription or translation [9].