Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1.
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.
Yung
E
E
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York, USA.
Sorin
M
M
Pal
A
A
Craig
E
E
Morozov
A
A
Delattre
O
O
Kappes
J
J
Ott
D
D
Kalpana
G V
GV
D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005799:Genes, Dominant; D015497:HIV-1 / Q000648:ultrastructure*; D006801:Humans; D000071796:SMARCB1 Protein; D014157:Transcription Factors; D014771:Virion / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D017931:DNA Primers; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors