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Transcriptional Reprogramming during Effector-to-Memory Transition Renders CD4+ T Cells Permissive for Latent HIV-1 Infection
Immunity ( IF 25.5 ) Pub Date : 2017-10-17 , DOI: 10.1016/j.immuni.2017.09.014
Liang Shan , Kai Deng , Hongbo Gao , Sifei Xing , Adam A. Capoferri , Christine M. Durand , S. Alireza Rabi , Gregory M. Laird , Michelle Kim , Nina N. Hosmane , Hung-Chih Yang , Hao Zhang , Joseph B. Margolick , Linghua Li , Weiping Cai , Ruian Ke , Richard A. Flavell , Janet D. Siliciano , Robert F. Siliciano

The latent reservoir for HIV-1 in resting memory CD4+ T cells is the major barrier to curing HIV-1 infection. Studies of HIV-1 latency have focused on regulation of viral gene expression in cells in which latent infection is established. However, it remains unclear how infection initially becomes latent. Here we described a unique set of properties of CD4+ T cells undergoing effector-to-memory transition including temporary upregulation of CCR5 expression and rapid downregulation of cellular gene transcription. These cells allowed completion of steps in the HIV-1 life cycle through integration but suppressed HIV-1 gene transcription, thus allowing the establishment of latency. CD4+ T cells in this stage were substantially more permissive for HIV-1 latent infection than other CD4+ T cells. Establishment of latent HIV-1 infection in CD4+ T could be inhibited by viral-specific CD8+ T cells, a result with implications for elimination of latent HIV-1 infection by T cell-based vaccines.



中文翻译:

效应器到记忆过渡过程中的转录重编程使潜在的HIV-1感染允许CD4 + T细胞。

静息记忆CD4 + T细胞中HIV-1的潜在储存库是治愈HIV-1感染的主要障碍。HIV-1潜伏期的研究集中于在建立潜伏感染的细胞中调节病毒基因表达。但是,目前尚不清楚感染最初是如何潜伏的。在这里,我们描述了经历效应子到内存过渡的CD4 + T细胞的一组独特属性,包括CCR5表达的暂时上调和细胞基因转录的快速下调。这些细胞通过整合完成了HIV-1生命周期中的步骤,但抑制了HIV-1基因的转录,从而建立了潜伏期。CD4 +与其他CD4 + T细胞相比,此阶段的T细胞对HIV-1潜在感染的允许更大。病毒特异性CD8 + T细胞可抑制CD4 + T中潜在HIV-1感染的建立,这一结果对消除基于T细胞的疫苗对HIV-1潜在感染的消除具有影响。

更新日期:2017-10-17
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