Insertion and deletion analyses identify regions of non-structural protein 5A of Hepatitis C virus that are dispensable for viral genome replication

Insertion and deletion analyses identify regions of non-structural protein 5A of Hepatitis C virus that are dispensable for viral genome replication
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DOI:
10.1099/vir.0.81407-0
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发表时间:
2006-02-01
影响因子:
3.8
通讯作者:
Pattnaik, AK
Pattnaik, AK
中科院分区:
医学3区
文献类型:
--
作者:
Liu, SH;Ansari, IH;Pattnaik, AK

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丙型肝炎病毒(HCV)非结构蛋白5A(NS 5A)在病毒基因组复制中起重要作用。利用一系列转座子介导的NS 5A插入突变体和缺失突变体检测编码突变蛋白的HCV亚基因组复制子的集落形成能力。结果表明,NS 5A的两个区域可以容忍插入:一个跨越残基240-314,其中包含干扰素敏感性决定区(ISDR),另一个跨越残基349-417在羧基末端。这些位点中的大多数也耐受增强型绿色荧光蛋白的插入。此外,在ISDR或羧基末端区域缺失的NS 5A编码复制子是可复制的,表明NS 5A的这些区域对于复制不是必需的。综上所述,结果表明,跨越ISDR的中心区域和分子的羧基末端区域与NS 5A在病毒基因组复制中的功能相关。
Hepatitis C virus (HCV) non-structural protein 5A (NS5A) plays an essential role in viral genome replication. A series of transposon-mediated insertion mutants and deletion mutants of NS5A was used to examine the colony-forming ability of HCV subgenomic replicons encoding the mutant proteins. The results reveal that two regions of NS5A can tolerate insertions: one spanning residues 240-314, which contain the interferon sensitivity-determining region (ISDR), and the other spanning residues 349-417 at the carboxy terminus. The majority of these sites also tolerated insertion of enhanced green fluorescent protein. Furthermore, replicons encoding NS5A with deletions in ISDR or in the carboxy-terminal regions were replication-competent, indicating that these regions of NS5A are not necessary for replication. Taken together, the results suggest that the central region spanning the ISDR and the carboxy-terminal region of the molecule are dispensable for the functions of NS5A in viral genome replication.