Lymph Node Cellular and Viral Dynamics in Natural Hosts and Impact for HIV Cure Strategies.
Lymph Node Cellular and Viral Dynamics in Natural Hosts and Impact for HIV Cure Strategies.
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DOI：
10.3389/fimmu.2018.00780
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发表时间：
2018
影响因子：
7.3
通讯作者：
Müller-Trutwin M
中科院分区：
文献类型：
--
作者：
Huot N;Bosinger SE;Paiardini M;Reeves RK;Müller-Trutwin M
联合抗逆转录病毒疗法（cART）有效地控制艾滋病毒复制，导致无法检测到的病毒血症和艾滋病毒感染者的寿命急剧增加。然而，cART不能治愈HIV感染，因为病毒持续存在于细胞和解剖学储库中，在cART停止后病毒通常很快从细胞和解剖学储库反弹。一个主要的解剖学储存库是淋巴结（LN）滤泡，其中HIV通过在滤泡辅助T细胞中复制而持续存在，并且也被滤泡树突细胞捕获。SIV的天然宿主，如非洲绿色猴和白眉猴，虽然表现出持续的高病毒血症，但通常不会发展为疾病。引人注目的是，这些主机安装一个强大的控制病毒复制LN滤泡后不久，病毒血症高峰，持续整个感染。在这里，我们讨论了潜在的相互作用之间的病毒控制淋巴结和炎症的决议，这是自然宿主的特点。我们还详细说明了存在于自然宿主中的非致病性SIV感染和人类和猕猴中的致病性HIV/SIV感染之间的差异，这些差异涉及病毒靶细胞和LN中的复制动力学。已提出多种机制与天然宿主淋巴结中病毒复制的强控制有关，例如NK细胞介导的控制，本文将对此进行综述，以及在天然宿主中进行的体内细胞耗竭研究的教训和局限性。最后，我们讨论的影响，这些见解的病毒动力学和宿主的反应，在LN的自然宿主的发展战略，艾滋病毒治愈。
Combined antiretroviral therapies (cARTs) efficiently control HIV replication leading to undetectable viremia and drastic increases in lifespan of people living with HIV. However, cART does not cure HIV infection as virus persists in cellular and anatomical reservoirs, from which the virus generally rebounds soon after cART cessation. One major anatomical reservoir are lymph node (LN) follicles, where HIV persists through replication in follicular helper T cells and is also trapped by follicular dendritic cells. Natural hosts of SIV, such as African green monkeys and sooty mangabeys, generally do not progress to disease although displaying persistently high viremia. Strikingly, these hosts mount a strong control of viral replication in LN follicles shortly after peak viremia that lasts throughout infection. Herein, we discuss the potential interplay between viral control in LNs and the resolution of inflammation, which is characteristic for natural hosts. We furthermore detail the differences that exist between non-pathogenic SIV infection in natural hosts and pathogenic HIV/SIV infection in humans and macaques regarding virus target cells and replication dynamics in LNs. Several mechanisms have been proposed to be implicated in the strong control of viral replication in natural host’s LNs, such as NK cell-mediated control, that will be reviewed here, together with lessons and limitations of in vivo cell depletion studies that have been performed in natural hosts. Finally, we discuss the impact that these insights on viral dynamics and host responses in LNs of natural hosts have for the development of strategies toward HIV cure.