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Journal of Virology, March 2004, p. 2222-2231, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2222-2231.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Specificity of Interaction of INI1/hSNF5 with Retroviral Integrases and Its Functional Significance

Eric Yung,1,{dagger} Masha Sorin,1,{dagger} Emilie-Jeanne Wang,1 Seena Perumal,1 David Ott,2 and Ganjam V. Kalpana1*

Department of Molecular Genetics, Albert Einstein College of Medicine, New York, New York 10461,1 AIDS Vaccine Program, SAIC-Frederick Inc., National Cancer Institute at Frederick, Maryland 217022

Received 31 July 2003/ Accepted 8 November 2003

Integrase interactor 1 (INI1)/hSNF5 is a host factor that directly interacts with human immunodeficiency virus type 1 (HIV-1) integrase and is incorporated into HIV-1 virions. Here, we show that while INI1/hSNF5 is completely absent from purified microvesicular fractions, it is specifically incorporated into HIV-1 virions with an integrase-to-INI1/hSNF5 stoichiometry of approximately 2:1 (molar ratio). In addition, we show that INI1/hSNF5 is not incorporated into related primate lentiviral and murine retroviral particles despite the abundance of the protein in producer cells. We have found that the specificity in incorporation of INI1/hSNF5 into HIV-1 virions is directly correlated with its ability to exclusively interact with HIV-1 integrase but not with other retroviral integrases. This specificity is also reflected in our finding that the transdominant mutant S6, harboring the minimal integrase interaction domain of INI1/hSNF5, blocks HIV-1 particle production but not that of the other retroviruses in 293T cells. Taken together, these results suggest that INI1/hNSF5 is a host factor restricted for HIV-1 and that S6 acts as a highly specific and potent inhibitor of HIV-1 replication.

* Corresponding author. Mailing address: Department of Molecular Genetics, Albert Einstein College of Medicine, 1300 Morris Park Ave., Ullman 821, Bronx, NY 10461. Phone: (718) 430-2354. Fax: (718) 430-8778. E-mail: kalpana{at}aecom.yu.edu.

{dagger} These authors contributed equally to this study.

Journal of Virology, March 2004, p. 2222-2231, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2222-2231.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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