Latently-infected CD4+ T Cells Are Enriched for HIV-1 Tat Variants with Impaired Transactivation Activity

Overview

Journal Virology

Specialty Microbiology

Date 2009 Mar 10

PMID 19268337

Citations 47

Authors

Steven Yukl

Satish Pillai

Peilin Li

Karen Chang

William Pasutti

Chris Ahlgren

Diane Havlir

Matthew Strain

Huldrych Gunthard

Douglas Richman

Andrew P Rice

Eric Daar

Susan Little

Joseph K Wong

Affiliations

Soon will be listed here.

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.

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