Elsevier

Virology

Volume 387, Issue 1, 25 April 2009, Pages 98-108
Virology

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

https://doi.org/10.1016/j.virol.2009.01.013Get rights and content
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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.

Keywords

HIV
Latency
Tat
Transcription
Transactivation
TAR
CD4
Early infection

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