Yukl, S; Pillai, S; Li, P; Chang, K; Pasutti, W; Ahlgren, C; Havlir, D; Strain, M; Günthard, H; Richman, D; Rice, A P; Daar, Eric; Little, S; Wong, J K (2009). Latently-infected CD4+ T cells are enriched for HIV-1 Tat variants with impaired transactivation activity. Virology, 387(1):98-108.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases|
|DDC:||610 Medicine & health|
|Deposited On:||20 Jan 2010 16:56|
|Last Modified:||28 Nov 2013 01:31|
|Citations:||Web of Science®. Times cited: 19|
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