Distinct biomarker signatures in HIV acute infection associate with viral dynamics and reservoir size
Distinct biomarker signatures in HIV acute infection associate with viral dynamics and reservoir size
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DOI：
10.1172/jci.insight.98420
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发表时间：
2018-05-17
期刊：
影响因子：
8
通讯作者：
Krebs, Shelly J.
中科院分区：
文献类型：
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作者：
Teigler, Jeffrey E.;Leyre, Louise;Krebs, Shelly J.
估计病毒储存库的大小对艾滋病毒治疗策略至关重要。外周循环中的生物标志物可能有助于了解不易进入的隔间中病毒库的建立。因此，我们测量了84种可溶性生物标志物的全身水平，这些标志物属于急性HIV感染中抗逆转录病毒治疗初期（ART-naive）个体和早期发现HIV感染后开始ART治疗的个体的广泛免疫途径。这些生物标志物在急性和慢性感染期间进行了纵向测量，并评估了它们与病毒库建立和持久性的关系。我们观察到HIV感染后诱导的几种不同的生物标志物途径，如ifn - γ信号趋化因子、促炎标志物和tnf - α家族成员。在急性HIV感染期间，这些因子的水平与同时的病毒载量和/或携带HIV DNA的外周血单个核细胞的频率直接相关。MCP-1、MIP-3 β、sTNFR-II和IL-10水平与治疗96周后HIV DNA水平相关，提示早期免疫信号事件与抗逆转录病毒治疗期间病毒库的建立和持续存在联系。此外，它们提供了潜在的新工具，可以深入了解急性感染个体的相对库大小以及治疗中断的潜在相关风险。
Estimating the size of the viral reservoir is critical for HIV cure strategies. Biomarkers in peripheral circulation may give insights into the establishment of the viral reservoir in compartments not easily accessible. We therefore measured systemic levels of 84 soluble biomarkers belonging to a broad array of immune pathways in acute HIV infection in both antiretroviral therapy-naive (ART-naive) individuals as well as individuals who began ART upon early detection of HIV infection. These biomarkers were measured longitudinally during acute and chronic infection and their relationship to viral reservoir establishment and persistence was assessed. We observed several distinct biomarker pathways induced following HIV infection such as IFN-gamma-signaled chemokines, proinflammatory markers, and TNF-alpha-family members. Levels of several of these factors directly correlated with contemporaneous viral loads and/or frequency of peripheral blood mononuclear cells harboring HIV DNA during acute HIV infection. MCP-1, MIP-3 beta, sTNFR-II, and IL-10 levels prior to ART associated with HIV DNA levels after 96 weeks of treatment, suggesting a link between early immune signaling events and the establishment and persistence of the viral reservoir during ART. Furthermore, they offer potentially novel tools for gaining insight into relative reservoir size in acutely infected individuals and the potential of associated risks of treatment interruption.