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Virology. 2009 Apr 25;387(1):98-108. doi: 10.1016/j.virol.2009.01.013. Epub 2009 Mar 5.

Latently-infected CD4+ T cells are enriched for HIV-1 Tat variants with impaired transactivation activity.

Author information

1
University of California, San Francisco (UCSF) and San Francisco VA Medical Center (SFVAMC), 4150 Clement Street, 111W3, San Francisco, CA 94121, USA. steven.yukl@ucsf.edu

Abstract

The ability of HIV to establish latent infection in CD4+ lymphocytes represents a major barrier to the eradication of HIV. It is not clear what mechanisms favor latent over productive infection, but prior studies have suggested a role for the viral transcription factor Tat or its RNA target, TAR. Using samples from five individuals who were started on ART within 6 months of infection and achieved a viral load <50 (suppressed), we isolated one- and two-exon tat RNA from HIV propagated ex vivo from baseline plasma and from co-cultures of CD4+ T cells obtained at baseline and suppressed time points. Compared to virus from the baseline plasma (mostly from productively-infected CD4+ T cells), virus from the baseline and suppressed co-cultures (mostly from latently-infected cells) had more Tat variants with impaired transactivation activity. These findings suggest that impaired activity in the Tat-TAR axis may contribute to the establishment of latent infection in CD4+ T cells.

PMID:
19268337
PMCID:
PMC4474533
DOI:
10.1016/j.virol.2009.01.013
[Indexed for MEDLINE]
Free PMC Article

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