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

Nature Medicine volume 7, pages 920–926 (2001)Cite this 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.

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Figure 1: S6 inhibits HIV-1 particle production and replication.
Figure 2: Interaction-defective mutants of S6 abrogate the inhibitory effect on viral particle production.
Figure 3: INI1-interaction–defective mutation in integrase abrogates the inhibitory effect of S6.
Figure 4: Sub-cellular localization of INI1 and the truncation mutants S6 and E3.
Figure 5: INI1 is required for efficient particle production and is encapsulated in virions.

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Acknowledgements

We thank V.R. Prasad and J. Brojatsch for critically reading the manuscript; R. Kim, R. Beltran, S-W. G. Cheng and P. Joshi for technical help; D. Helland and D. Trono for reagents; S. Goff for helpful discussions; and A. Rubinstein, Y. Mizrachi, M. Mantovani, G. Liu and N. Sokolov for assistance with the p24 ELISA assays. This work was funded by a NIH grant AI/GM 399951 to G.V.K. and a contract NOI-CO-56000 to D.O. M.S. and A.P. were funded by an institutional training grant T32-AI07501

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Authors and Affiliations

  1. Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York, USA

    Eric Yung, Masha Sorin, Achintya Pal, Errol Craig, Alexei Morozov & Ganjam V. Kalpana

  2. AIDS Vaccine Program, SAIC-Frederick, National Cancer Institute-Frederick, Frederick, Maryland, USA

    David Ott

  3. Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA

    John Kappes

  4. Laboratoire de Pathologie Moleculaire des Cancers, Institut Curie, Paris, France

    Olivier Delattre

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Correspondence to Ganjam V. Kalpana.

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Yung, E., Sorin, M., Pal, A. et al. Inhibition of HIV-1 virion production by a transdominant mutant of integrase interactor 1. Nat Med 7, 920–926 (2001). https://doi.org/10.1038/90959

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