Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1

被引:110
作者
Yung, E
Sorin, M
Pal, A
Craig, E
Morozov, A
Delattre, O
Kappes, J
Oti, D
Kalpana, GV [1 ]
机构
[1] Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA
[2] NCI, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA
[3] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA
[4] Inst Curie, Lab Pathol Mol Canc, Paris, France
关键词
D O I
10.1038/90959
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
Integase Interactor 1(INI), also known as hSNF5, is a protein that interacts with HIV-1 integrase. We report here that a cytoplasmically localized fragment of INI (S6; aa183-294) containing the minimal integrase-interaction domain potently inhibits HIV-1 particle production and replication. Mutations in 56 or integrase that disrupt integrase-INI1 interaction abrogated the inhibitory effect. An integrase-deficient HIV-1 transcomplemented with integrase fused to Vpr was not affected by S6. INI1 was specifically incorporated into virions and was required for efficient HIV-1 particle production. These results indicate that INI1 is required for late events in the viral life cycle, and that ectopic expression of S6 inhibits HIV-1 replication in a transdominant manner via its specific interaction with integrase within the context of Gag-Pol, providing a novel strategy to control HIV-1 replication.
引用
收藏
页码:920 / 926
页数:7
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