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

Latently-infected CD4+ T cells are enriched for HIV-1 Tat variants with impaired transactivation activity.
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DOI:
10.1016/j.virol.2009.01.013
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发表时间:
2009-04-25
期刊:
影响因子:
3.7
通讯作者:
Wong JK
Wong JK
中科院分区:
医学3区
文献类型:
--
作者:
Yukl S;Pillai S;Li P;Chang K;Pasutti W;Ahlgren C;Havlir D;Strain M;Günthard H;Richman D;Rice AP;Daar E;Little S;Wong JK

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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.
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