AIDSWEEKLY Plus; Monday, December 6, 2004
Staff Medical Writers

"To design strategies to purge latent reservoirs of human immunodeficiency virus type 1 (HrV-1), we investigated mechanisms by which a non-tumor-promoting phorbol ester, prostratin, inhibits infection of CD4+ T lymphocytes and at the same time reactivates virus from latency," scientists in France report.

"CD4+ T lymphocytes from primary blood mononuclear cells (PBMC) and in blocks of human lymphoid tissue were stimulated with prostratin and infected with HIV-1 to investigate the effects of prostratin on cellular susceptibility to the virus.

"The capacity of prostratin to reactivate HIV from latency was tested in CD4+ T cells harboring preintegrated and integrated latent provirus," said A. Biancotto and coworkers.

"Prostratin stimulated CD4+ T cells in an aberrant way. It induced expression of the activation markers CD25 and CD69 but inhibited cell cycling. HIV-1 uptake was reduced in prostratin-stimulated CD4+ T PBMC and tissues in a manner consistent with a downregulation of CD4 and CXCR4 receptors in these systems.

"At the postentry level," investigators wrote, "prostratin inhibited completion of reverse transcription of the viral genome in lymphoid tissue. However, prostratin facilitated integration of the reverse-transcribed HIV-1 genome in nondividing CD4+ T cells and facilitated expression of already integrated HIV-1, including latent forms."

"Thus, while stimulation with prostratin restricts susceptibility of primary resting CD4+ T cells to HIV infection at the virus cell-entry level and at the reverse transcription level," Biancotto concluded, "it efficiently reactivates HIV-1 from pre- and postintegration latency in resting CD4+ T cells."

Biancotto and colleagues published their study in the Journal of Virology (Dual role of prostratin in inhibition of infection and reactivation of human immunodeficiency virus from latency in primary blood lymphocytes and lymphoid tissue. J Virol. 2004 Oct;78(19):10507-15.

For additional information, contact I. Hirsch, INSERM, U372, Laboratory Pathogenie Infection Lentivirus, 163 Avenue Luminy, BP 178, Parc Science & Technology Luminy, F-13276 Marseille 9, France.

The publisher's contact information for the Journal of Virology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

The information in this article comes under the major subject areas of Prostratin, HIV/AIDS, Genomics & Genetics, Pathogenesis and Immunology.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Biancotto A, Grivel JC, Gondois-Rey F, et al., "Dual role of prostratin in inhibition of infection and reactivation of human immunodeficiency virus from latency in primary blood lymphocytes and lymphoid tissue", J Virol. 2004 Oct;78(19):10507-15.

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