Yukl Steven, Pillai Satish, Li Peilin, Chang Karen, Pasutti William, Ahlgren Chris, Havlir Diane, Strain Matthew, Günthard Huldrych, Richman Douglas, Rice Andrew P, Daar Eric, Little Susan, Wong Joseph K
University of California, San Francisco (UCSF) and San Francisco VA Medical Center (SFVAMC), 4150 Clement Street, 111W3, San Francisco, CA 94121, USA.
Virology. 2009 Apr 25;387(1):98-108. doi: 10.1016/j.virol.2009.01.013. Epub 2009 Mar 5.
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.
HIV在CD4+淋巴细胞中建立潜伏感染的能力是根除HIV的主要障碍。目前尚不清楚哪些机制有利于潜伏感染而非增殖性感染，但先前的研究表明病毒转录因子Tat或其RNA靶标TAR发挥了作用。我们使用了5名在感染后6个月内开始接受抗逆转录病毒治疗（ART）且病毒载量<50（被抑制）的个体的样本，从基线血浆以及在基线和病毒载量被抑制时间点获得的CD4+ T细胞共培养物中体外增殖的HIV中分离出单外显子和双外显子tat RNA。与来自基线血浆的病毒（主要来自增殖性感染的CD4+ T细胞）相比，来自基线和病毒载量被抑制的共培养物的病毒（主要来自潜伏感染的细胞）具有更多反式激活活性受损的Tat变体。这些发现表明，Tat-TAR轴活性受损可能有助于CD4+ T细胞中潜伏感染的建立。
