Altered T-cell subset distribution in the viral reservoir in HIV-1-infected individuals with extremely low proviral DNA (LoViReTs).
Altered T-cell subset distribution in the viral reservoir in HIV-1-infected individuals with extremely low proviral DNA (LoViReTs).
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DOI：
10.1111/joim.13484
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发表时间：
2022-08
影响因子：
11.1
通讯作者：
Salgado, Maria
中科院分区：
文献类型：
--
作者：
Galvez, Cristina;Urrea, Victor;del Carmen Garcia-Guerrero, Maria;Bernal, Silvia;Benet, Susana;Mothe, Beatriz;Bailon, Lucia;Dalmau, Judith;Martinez, Andrea;Nieto, Aroa;Leal, Lorna;Garcia, Felipe;Clotet, Bonaventura;Martinez-Picado, Javier;Salgado, Maria
艾滋病毒治疗战略旨在消除尽管抗逆转录病毒疗法(ART)取得成功但仍存在的病毒库。我们之前已经描述过，接受抗逆转录病毒治疗的艾滋病毒感染者中有9%患有低水平的前病毒(LoVirets)。我们选择了22个与ART抑制3年以上的对照相匹配的LoViRet，分别有不到100个和100个以上的HIV-DNA拷贝/106个CD4+T细胞。我们测量了血液和宿主遗传因素中的艾滋病毒储备库。14名LoViRet患者接受了白细胞分离，以分析CD4+T细胞亚群中具有复制能力的病毒和HIV-DNA。此外，我们还检测了其中9例患者的直肠和/或淋巴组织中的HIV-DNA。我们发现，与对照组相比，LoViRets不仅拥有更低的总HIV-DNA水平，而且显著降低了完整的HIV-DNA、细胞相关的HIV-RNA和超敏感的病毒载量。在两组中，完整的前病毒占总前病毒的比例相似。我们发现宿主因素的百分比没有差异。在外周血中，71%的LoViRet具有无法检测到的复制能力病毒。与接受抗逆转录病毒治疗的HIV感染者相比，直肠和淋巴活检中发现了最低水平的总HIV-DNA。病毒储存库的主要贡献者是短暂的过渡性记忆T细胞和效应记忆T细胞(分别为47%和29%)，这表明HIV储存库在LoViRets的外周T细胞亚群中的分布发生了变化。综上所述，LoViRets的特点是外周血和次级淋巴组织中低水平的病毒库，这可能是由于前病毒HIV-DNA的分布改变，倾向于更短暂的记忆T细胞。LoViRets可以被认为是未来旨在治愈艾滋病毒的干预措施的特殊候选者。
HIV cure strategies aim to eliminate viral reservoirs that persist despite successful antiretroviral therapy (ART). We have previously described that 9% of HIV‐infected individuals who receive ART harbor low levels of provirus (LoViReTs). We selected 22 LoViReTs matched with 22 controls ART suppressed for more than 3 years with fewer than 100 and more than 100 HIV‐DNA copies/106 CD4+ T cells, respectively. We measured HIV reservoirs in blood and host genetic factors. Fourteen LoViReTs underwent leukapheresis to analyze replication‐competent virus, and HIV‐DNA in CD4+ T‐cell subpopulations. Additionally, we measured HIV‐DNA in rectum and/or lymph node biopsies from nine of them. We found that LoViReTs harbored not only lower levels of total HIV‐DNA, but also significantly lower intact HIV‐DNA, cell‐associated HIV‐RNA, and ultrasensitive viral load than controls. The proportion of intact versus total proviruses was similar in both groups. We found no differences in the percentage of host factors. In peripheral blood, 71% of LoViReTs had undetectable replication‐competent virus. Minimum levels of total HIV‐DNA were found in rectal and lymph node biopsies compared with HIV‐infected individuals receiving ART. The main contributors to the reservoir were short‐lived transitional memory and effector memory T cells (47% and 29%, respectively), indicating an altered distribution of the HIV reservoir in the peripheral T‐cell subpopulations of LoViReTs. In conclusion, LoViReTs are characterized by low levels of viral reservoir in peripheral blood and secondary lymphoid tissues, which might be explained by an altered distribution of the proviral HIV‐DNA towards more short‐lived memory T cells. LoViReTs can be considered exceptional candidates for future interventions aimed at curing HIV.
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影响因子：
11.1
作者：
Ananworanich, Jintanat;Chomont, Nicolas;Eller, Leigh Ann;Kroon, Eugene;Tovanabutra, Sodsai;Bose, Meera;Nau, Martin;Fletcher, James L. K.;Tipsuk, Somporn;Vandergeeten, Claire;O'Connell, Robert J.;Pinyakorn, Suteeraporn;Michael, Nelson;Phanuphak, Nittaya;Robb, Merlin L.
通讯作者：
Robb, Merlin L.
影响因子：
16.6
作者：
Kinloch NN;Ren Y;Conce Alberto WD;Dong W;Khadka P;Huang SH;Mota TM;Wilson A;Shahid A;Kirkby D;Harris M;Kovacs C;Benko E;Ostrowski MA;Del Rio Estrada PM;Wimpelberg A;Cannon C;Hardy WD;MacLaren L;Goldstein H;Brumme CJ;Lee GQ;Lynch RM;Brumme ZL;Jones RB
通讯作者：
Jones RB
影响因子：
15.3
作者：
Macallan, DC;Wallace, D;Zhang, Y;de Lara, C;Worth, AT;Ghattas, H;Griffin, GE;Beverley, PCL;Tough, DE
通讯作者：
Tough, DE
影响因子：
64.8
作者：
Jiang C;Lian X;Gao C;Sun X;Einkauf KB;Chevalier JM;Chen SMY;Hua S;Rhee B;Chang K;Blackmer JE;Osborn M;Peluso MJ;Hoh R;Somsouk M;Milush J;Bertagnolli LN;Sweet SE;Varriale JA;Burbelo PD;Chun TW;Laird GM;Serrao E;Engelman AN;Carrington M;Siliciano RF;Siliciano JM;Deeks SG;Walker BD;Lichterfeld M;Yu XG
通讯作者：
Yu XG
影响因子：
6.4
作者：
Günthard, HF;Havlir, DV;Wong, JK
通讯作者：
Wong, JK