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

Academic Article

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.
  • Published In

  • Nature Medicine  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 18689453
  • Author List

  • Yung E; Sorin M; Pal A; Craig E; Morozov A; Delattre O; Kappes J; Ott D; Kalpana GV
  • Start Page

  • 920
  • End Page

  • 926
  • Volume

  • 7
  • Issue

  • 8