Reverse genetic analysis of a putative, influenza virus M2 HXXXW-like motif in the p7 protein of hepatitis C virus

被引：19
作者：
Meshkat, Z. [1 ]
Audsley, M. [1 ,2 ]
Beyer, C. [1 ]
Gowans, E. J. [1 ,2 ]
Haqshenas, G. [1 ,2 ]
机构：
[1] Macfarlane Burnet Inst, Melbourne, Vic, Australia
[2] Monash Univ, Dept Microbiol, Clayton, Vic 3168, Australia
来源：
JOURNAL OF VIRAL HEPATITIS | 2009年 / 16卷 / 03期
基金：
英国医学研究理事会;
关键词：
hepatitis C virus; HXXXW motif; influenza virus; M2; p7; ION-CHANNEL ACTIVITY; TRANSMEMBRANE DOMAIN; PROTON CHANNEL; REPLICATION; LOCALIZATION; POLYPEPTIDE; AMANTADINE; GATE;
D O I：
10.1111/j.1365-2893.2008.01064.x
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
The p7 protein of hepatitis C virus (HCV) has been classified into a family of viral proteins, designated viroporins that form ion channels. The M2 protein of influenza virus is the prototype viroporin and encodes a HXXXW motif that constitutes the main functional element of the M2 channels. Alignment of different p7 proteins revealed that a HXXXW sequence (positions 17-21) is also highly conserved among some HCV genotypes. To study the putative HXXXW motif in p7, five mutants of the Japanese fulminant hepatitis 1 strain of HCV that encoded H17A, H17G, H17E, Y21A and Y21W were generated. After transfection of human hepatoma cells with the mutant transcripts, unlike H17A and H17G that produced up to 1 log lower viral titres than wild type, H17E and Y21W showed slightly higher infectivity. In conclusion, this study demonstrated that the HXXXW sequence exists in the p7 proteins of some HCV genotypes and that H17 plays an important role in virus replication.
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收藏
页码：187 / 194
页数：8
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