THE CENTRAL GLOBULAR DOMAIN OF THE NUCLEOCAPSID PROTEIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IS CRITICAL FOR VIRION STRUCTURE AND INFECTIVITY

被引:98
作者
OTTMANN, M
GABUS, C
DARLIX, JL
机构
[1] ECOLE NORMALE SUPER LYON,INSERM,U412,UNITE ONCOL HUMAINE,F-69364 LYON 07,FRANCE
[2] ECOLE NORMALE SUPER LYON,INSERM,U412,UNITE VIROL HUMAINE,LABORETRO,F-69364 LYON 07,FRANCE
关键词
D O I
10.1128/JVI.69.3.1778-1784.1995
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The nucleocapsid protein NCp7 of human immunodeficiency virus type 1 (HIV-1) is a 72-amino-acid peptide containing two CCHC-type zinc fingers linked by a short basic sequence, (29)RAPRKKG(35), which is conserved in HIV-1 and simian immunodeficiency virus, The complete three-dimensional structure of NCp7 has been determined by H-1-nuclear magnetic resonance spectroscopy (N. Morellet, H. de Rocquigny, Y. Mely, N. Jullian, H. Demene, M. Ottmann, D. Gerard, J. L. Darlix, M. C. Fourni-Zaluski, and B. P. Rogues, J. Mol. Biol. 235:287-301, 1994) and revealed a central globular domain where the two zinc fingers are brought in close proximity by the RAPRKKG linker, To examine the role of this globular structure and more precisely of the RAPRKKG linker in virion structure and infectivity, we generated HIV-1 DNA mutants in the RAPRKK sequence of NCp7 and analyzed the mutant virions produced by transfected cells, Mutations that probably alter the structure of NCp7 structure led to the formation of very poorly infectious virus (A30P) or noninfectious virus (P31L and R32G). In addition, the P31L mutant did not contain detectable amounts of reverse transcriptase and had an immature core morphology, as determined by electron microscopy. On the other hand, mutations changing the basic nature of NCp7 had poor effect, R29S had a wild-type phenotype, and the replacement of (32)RKK(34) by SSS (S3 mutant) resulted in a decrease by no more than 100-fold of the virus titer. These results clearly show that the RAPRKKG linker contains residues that are critical for virion structure and infectivity.
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页码:1778 / 1784
页数:7
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