High multiplicity HIV-1 cell-to-cell transmission from macrophages to CD4+ T cells limits antiretroviral efficacy.
High multiplicity HIV-1 cell-to-cell transmission from macrophages to CD4+ T cells limits antiretroviral efficacy.
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DOI：
10.1097/qad.0b013e3283632ec4
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发表时间：
2013-09-10
期刊：
影响因子：
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通讯作者：
Sattentau QJ
中科院分区：
文献类型：
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作者：
Duncan CJ;Russell RA;Sattentau QJ
目的：很少有研究探讨抗逆转录病毒治疗（ART）在细胞间传播的背景下的疗效。我们的目的是要确定是否ART的活动是有限的HIV-1传播的细胞和类型的免疫细胞之间的transmission.Design：ART活性进行了评估，在原代细胞使用在体外无细胞和细胞对细胞HIV-1 infection systems.Methods：HIV-1无细胞或细胞对细胞之间的传输感染的单核细胞衍生的巨噬细胞（MDM）和自体靶CD 4 + T细胞进行了测量，在存在或不存在的逆转录酶和整合酶抑制剂。使用携带嗜巨噬细胞包膜糖蛋白（Envs）的报告酶感染性分子HIV-1克隆评价病毒感染。无细胞的HIV-1滴定产生不同的多样性的CD 4 + T细胞infection.Results：而无细胞感染的CD 4 + T细胞大大减少了所有抑制剂，细胞到细胞的传播，从巨噬细胞的CD 4 + T细胞在很大程度上耐抑制。然而，当多重感染被控制，我们没有观察到细胞间或无细胞infection.Conclusion抗逆转录病毒抑制的差异：细胞间传播的HIV-1降低了抗逆转录病毒抑制的概率，但它是细胞之间转移的感染性病毒的数量，而不是特定的病毒传播模式或传输细胞类型，管理抗逆转录病毒活性。体内高多重性感染更可能通过细胞间传播发生，这些数据将为抗病毒药物的使用提供信息。
Objective:Few studies have examined the efficacy of antiretroviral therapy (ART) in the context of cell-to-cell transmission. We aimed to determine whether the activity of ART is limited by the mode of HIV-1 spread between cells and the type of immune cell implicated in transmission, or is independent of these variables.Design:ART activity was evaluated in primary cells using in-vitro cell-free and cell to-cell HIV-1 infection systems.Methods:HIV-1 cell-free or cell-to-cell transmission between infected monocyte-derived macrophages (MDMs) and autologous target CD4+ T cells was measured in the presence or absence of reverse transcriptase and integrase inhibitors. Viral infection was evaluated using luciferase-reporter infectious molecular HIV-1 clones carrying macrophage-tropic envelope glycoproteins (Envs). Cell-free HIV-1 was titrated to yield different multiplicities of CD4+ T-cell infection.Results:Whereas cell-free infection of CD4+ T cells was substantially reduced by all inhibitors, cell-to-cell spread from macrophages to CD4+ T cells was largely resistant to inhibition. However, when multiplicity of infection was controlled for, we observed no difference in antiretroviral inhibition of cell-to-cell or cell-free infection.Conclusion:Cell-to-cell spread of HIV-1 reduces the probability of antiretroviral inhibition, but it is the number of infectious viruses transferred between cells rather than the specific mode of viral spread or transmitting cell type that governs antiretroviral activity. High multiplicity infection in vivo is more likely to occur by cell-to-cell transmission, and these data will inform use of ART against viral reservoirs.