THE HEPATITIS-C VIRUS ENCODES A SERINE PROTEASE INVOLVED IN PROCESSING OF THE PUTATIVE NONSTRUCTURAL PROTEINS FROM THE VIRAL POLYPROTEIN PRECURSOR

被引:170
作者
ECKART, MR [1 ]
SELBY, M [1 ]
MASIARZ, F [1 ]
LEE, C [1 ]
BERGER, K [1 ]
CRAWFORD, K [1 ]
KUO, C [1 ]
KUO, G [1 ]
HOUGHTON, M [1 ]
CHOO, QL [1 ]
机构
[1] CHIRON CORP,4560 HORTON ST,EMERYVILLE,CA 94508
关键词
D O I
10.1006/bbrc.1993.1429
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The hepatitis C virus (HCV) nonstructural protein 3 (NS3) domain has been predicted from sequence comparisons to represent a trypsin-like serine protease. By expressing wild-type and mutant HCV-1 cDNAs in transfected mammalian cells, we have identified putative nonstructural proteins 3 (72 kDa), 4 (10 kDa and 27 kDa) and 5 (58 kDa) and have shown that their processing from the viral polyprotein precursor is dependent on Ser1165 located in the proposed protease catalytic site. Data obtained from in vitro RNA translations indicate that unlike the processing of the NS2/NS3 junction, NS3/NS4 processing is dependent on Ser1165. In contrast to the situation for the related flaviviral NS3 proteases, the HCV NS3-mediated cleavage of the NS3/NS4 junction does not require the upstream NS2 domain and may not occur at dibasic sites. © 1993 Academic Press, Inc.
引用
收藏
页码:399 / 406
页数:8
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