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Journal of Virology, August 2002, p. 8118-8123, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8118-8123.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Effects of Prostratin on T-Cell Activation and Human Immunodeficiency Virus Latency

Yael D. Korin,1 David G. Brooks,2 Stephen Brown,3 Andrew Korotzer,3 and Jerome A. Zack1,2*

Departments of Medicine,1 Microbiology, Immunology and Molecular Genetics, UCLA School of Medicine, and UCLA AIDS Institute, Los Angeles, California 90095-1678,2 AIDS Research Alliance, West Hollywood, California 900693

Received 5 December 2001/ Accepted 9 May 2002

Human immunodeficiency virus (HIV) replication is linked to cellular gene transcription and requires target cell activation. The latent reservoir of HIV-1 in quiescent T cells is thought to be a major obstacle to clearance of infection by highly active antiretroviral therapy (HAART). Thus, identification of agents that can induce expression of latent virus may, in the presence of HAART, allow elimination of the infected cells by the immune response. We previously used the SCID-hu (Thy/Liv) mouse model to establish that activation-inducible HIV can be generated at high frequency during thymopoiesis. Latently infected mature thymocytes can be exported into the periphery, providing an efficient primary cell model to determine cellular activation signals that induce renewed expression of latent virus. Here we characterized the effects of prostratin, a non-tumor-promoting phorbol ester, on primary human peripheral blood lymphocytes (PBLs) and assessed its ability to reactivate latent HIV infection from thymocytes and PBLs in the SCID-hu (Thy/Liv) model. Prostratin stimulation alone did not induce proliferation of quiescent PBLs; however, it could provide a secondary signal in the context of T-cell receptor stimulation or a primary activation signal in the presence of CD28 stimulation to induce T-cell proliferation. While prostratin alone was not sufficient to allow de novo HIV infection, it efficiently reactivated HIV expression from latently infected cells generated in the SCID-hu mouse. Our data indicate that prostratin alone is able to specifically reactivate latent virus in the absence of cellular proliferation, making it an attractive candidate for further study as an adjunctive therapy for the elimination of the latent HIV reservoir.

* Corresponding author. Mailing address: UCLA AIDS Institute, UCLA School of Medicine, 11-934 Louis Factor Bldg., 10833 Le Conte Ave., Los Angeles, CA 90095-1678. Phone: (310) 794-7765. Fax: (310) 794-6192. E-mail: jzack{at}ucla.edu.

Journal of Virology, August 2002, p. 8118-8123, Vol. 76, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.16.8118-8123.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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