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

  1. Author:
    Yung, E.
    Sorin, M.
    Pal, A.
    Craig, E.
    Morozov, A.
    Delattre, O.
    Kappes, J.
    Oti, D.
    Kalpana, G. V.

  2. Author Address

    Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. NCI, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Inst Curie, Lab Pathol Mol Canc, Paris, France. Kalpana GV Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA.
    1. Year: 2001
  2. Journal: Nature Medicine
    1. 7
    2. 8
    3. Pages: 920-926
  4. Type of Article: Article
  1. Abstract:

    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.

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