Initial productive and latent HIV infections originate in vivo by infection of resting T cells.
Initial productive and latent HIV infections originate in vivo by infection of resting T cells.
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DOI：
10.1172/jci171501
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发表时间：
2023-11-15
影响因子：
15.9
通讯作者：
Haase, Ashley T.
中科院分区：
文献类型：
--
作者：
Wietgrefe, Stephen W.;Anderson, Jodi;Duan, Lijie;Southern, Peter J.;Zuck, Paul;Wu, Guoxin;Howell, Bonnie J.;Reilly, Cavan;Kroon, Eugene;Chottanapund, Suthat;Buranapraditkun, Supranee;Sacdalan, Carlo;Tulmethakaan, Nicha;Colby, Donn J.;Chomchey, Nitiya;Prueksakaew, Peeriya;Pinyakorn, Suteeraporn;Trichavaroj, Rapee;Mitchell, Julie L.;Trautmann, Lydie;Hsu, Denise;Vasan, Sandhya;Manasnayakorn, Sopark;de Souza, Mark;Tovanabutra, Sodsai;Schuetz, Alexandra;Robb, Merlin L.;Phanuphak, Nittaya;Ananworanich, Jintanat;Schacker, Timothy W.;Haase, Ashley T.
生产性感染的细胞通常被认为是由活化的CD4+ T细胞的HIV感染引起的，并且这些感染的活化细胞被认为是当一部分群体转变为静息状态时潜伏感染细胞的重复来源。我们在这里发现并报告，生产性和潜伏性感染的细胞可以来自Fiebig I淋巴组织中静息CD4+ T细胞群的直接感染，这是可检测到的HIV感染的最早阶段。我们发现静息CD4+ T细胞的直接感染与淋巴组织中易感靶细胞的可用性相关，主要限于静息CD4+ T细胞，其中pTEFb的表达使生产性感染成为可能，并且我们记录了抗逆转录病毒治疗（ART）期间产生HIV的静息T细胞的持续性。因此，我们提供了一种机制的证据，通过该机制，直接感染淋巴组织中的静息T细胞以产生高效和潜伏感染的细胞，从而创建了一种机制，通过该机制，高效感染的细胞可以补充两个群体并维持两个病毒来源，HIV感染可以从中反弹，即使ART是在可检测感染的最早阶段开始的。
Productively infected cells are generally thought to arise from HIV infection of activated CD4+ T cells, and these infected activated cells are thought to be a recurring source of latently infected cells when a portion of the population transitions to a resting state. We discovered and report here that productively and latently infected cells can instead originate from direct infection of resting CD4+ T cell populations in lymphoid tissues in Fiebig I, the earliest stage of detectable HIV infection. We found that direct infection of resting CD4+ T cells was correlated with the availability of susceptible target cells in lymphoid tissues largely restricted to resting CD4+ T cells in which expression of pTEFb enabled productive infection, and we documented persistence of HIV-producing resting T cells during antiretroviral therapy (ART). Thus, we provide evidence of a mechanism by which direct infection of resting T cells in lymphoid tissues to generate productively and latently infected cells creates a mechanism by which the productively infected cells can replenish both populations and maintain two sources of virus from which HIV infection can rebound, even if ART is instituted at the earliest stage of detectable infection.
影响因子：
4.2
作者：
Ramakrishnan R;Chiang K;Liu H;Budhiraja S;Donahue H;Rice AP
通讯作者：
Rice AP
影响因子：
5.2
作者：
Wu G;Cheney C;Huang Q;Hazuda DJ;Howell BJ;Zuck P
通讯作者：
Zuck P