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

Eric Yung, Masha Sorin, Achintya Pal, Errol Craig, Alexei Morozov, Olivier Delattre, John Kappes, David Ott, Ganjam V. Kalpana

Research output: Contribution to journalArticle

117 Scopus citations

Abstract

Integase interactor 1 (INI1), also known as hSNF5, is a protein that interacts with HIV-1 integrase. We report here that a cytoplasmically localized fragment of INI1 (S6; aa183-294) containing the minimal integrase-interaction domain potently inhibits HIV-1 particle production and replication. Mutations in S6 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.

Original languageEnglish (US)
Pages (from-to)920-926
Number of pages7
JournalNature Medicine
Volume7
Issue number8
DOIs
StatePublished - Aug 29 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Yung, E., Sorin, M., Pal, A., Craig, E., Morozov, A., Delattre, O., Kappes, J., Ott, D., & Kalpana, G. V. (2001). Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1. Nature Medicine, 7(8), 920-926. https://doi.org/10.1038/90959