Selective inhibition of HIV replication in primary macrophages but not T lymphocytes by macrophage-derived chemokine
Selective inhibition of HIV replication in primary macrophages but not T lymphocytes by macrophage-derived chemokine
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DOI：
10.1073/pnas.160359197
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发表时间：
2000-08-01
影响因子：
11.1
通讯作者：
Poli, G
中科院分区：
文献类型：
--
作者：
Cota, M;Mengozzi, M;Poli, G
据报道，巨噬细胞衍生的趋化因子 (MDC) 可抑制激活的外周血单核细胞（T 细胞母细胞）中的不同 HIV-1 毒株，尽管其他研究人员尚未证实这些发现。在这里，我们证明 MDC 抑制单核细胞来源的巨噬细胞 (MDM) 中 CCR5 依赖性 (R5) HIV-1(BaL) 的复制，但不抑制 T 细胞母细胞的复制，尽管其效力取决于供体的变异性。 MDM 中 HIV-1(BaL) 前病毒 DNA 合成的分析表明，MDC 的抑制作用并不涉及早期事件的抑制，例如进入或逆转录。最后，观察到不同供体的未感染 MDM 分泌的内源性 MDC 水平与不同 HIV 毒株（包括具有不同辅助受体用途的两种初级分离株）在这些细胞中复制的效率之间存在负相关。因此，MDC代表了抑制巨噬细胞中HIV复制的趋化因子的一个例子，其在病毒生命周期中的一个或多个进入后水平发挥作用。
Macrophage-derived chemokine (MDC) has been reported to inhibit different HIV-1 strains in activated peripheral blood mononuclear cells (T cell blasts), although other investigators have not confirmed these findings. Here we demonstrate that MDC inhibits the replication of CCR5-dependent (R5) HIV-1(BaL) in monocyte-derived macrophages (MDM), but not in T cell blasts, although with variable potency depending on donor variability. Analysis of HIV-1(BaL) proviral DNA synthesis in MDM indicated that the suppressive effect of MDC did not involve inhibition of early events such as entry or reverse transcription. Finally, an inverse correlation was observed between the levels of endogenous MDC secreted by uninfected MDM of different donors and the efficiency of different HIV strains, including two primary isolates with different coreceptor usage, to replicate in these cells. Thus, MDC represents an example of a chemokine inhibiting HIV replication in macrophages acting at one or more postentry levels in the virus life cycle.