Dual role of prostratin in inhibition of infection and reactivation of human immunodeficiency virus from latency in primary blood lymphocytes and lymphoid tissue

Angélique Biancotto, Jean-Charles B. Grivel, Françoise Gondois-Rey, Lise Bettendroffer, Robert Vigne, Stephen Brown, Leonid B. Margolis, Ivan Hirsch

Research output: Contribution to journalArticle

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Abstract

To design strategies to purge latent reservoirs of human immunodeficiency virus type 1 (HIV-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. 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. 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, 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, it efficiently reactivates HIV-1 from pre- and postintegration latency in resting CD4+ T cells.

Original languageEnglish
Pages (from-to)10507-10515
Number of pages9
JournalJournal of Virology
Volume78
Issue number19
DOIs
Publication statusPublished - Oct 2004
Externally publishedYes

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Virus Latency
Lymphoid Tissue
HIV
Lymphocytes
HIV-1
T-Lymphocytes
Infection
Reverse Transcription
Blood Cells
CXCR4 Receptors
prostratin
Proviruses
Virus Internalization
CD4 Antigens
Viral Genome
Phorbol Esters
HIV Infections
Down-Regulation
Genome
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Dual role of prostratin in inhibition of infection and reactivation of human immunodeficiency virus from latency in primary blood lymphocytes and lymphoid tissue. / Biancotto, Angélique; Grivel, Jean-Charles B.; Gondois-Rey, Françoise; Bettendroffer, Lise; Vigne, Robert; Brown, Stephen; Margolis, Leonid B.; Hirsch, Ivan.

In: Journal of Virology, Vol. 78, No. 19, 10.2004, p. 10507-10515.

Research output: Contribution to journalArticle

Biancotto, Angélique ; Grivel, Jean-Charles B. ; Gondois-Rey, Françoise ; Bettendroffer, Lise ; Vigne, Robert ; Brown, Stephen ; Margolis, Leonid B. ; Hirsch, Ivan. / Dual role of prostratin in inhibition of infection and reactivation of human immunodeficiency virus from latency in primary blood lymphocytes and lymphoid tissue. In: Journal of Virology. 2004 ; Vol. 78, No. 19. pp. 10507-10515.
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