HIV-1 recognition by, interaction with, and/or infection of CD4(+)CCR5(+) tissue macrophages and dendritic cells (DCs) play important roles in HIV-1 transmission and pathogenesis. By comparison, circulating CD4(+)CCR5(+) monocytes appear relatively resistant to HIV-1, and a fundamental unresolved question involves deciphering restriction factors unique to this precursor population. Not only do monocytes, relative to macrophages, possess higher levels of the innate resistance factor APOBEC3G, but we uncovered APOBEC3A, not previously associated with anti-HIV activity, as being critical in monocyte resistance. Inversely correlated with susceptibility, silencing of APOBEC3A renders monocytes vulnerable to HIV-1. Differences in promiscuity of monocytes, macrophages, and DCs can be defined, at least partly, by disparities in APOBEC expression, with implications for enhancing cellular defenses against HIV-1.

中文翻译：

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骨髓分化和对 HIV-1 的易感性与 APOBEC3 表达相关


CD4(+)CCR5(+)组织巨噬细胞和树突状细胞(DC)对HIV-1的识别、相互作用和/或感染在HIV-1传播和发病机制中发挥着重要作用。相比之下，循环CD4(+)CCR5(+)单核细胞似乎对HIV-1具有相对抵抗力，而一个尚未解决的基本问题涉及破译该前体群体特有的限制因素。相对于巨噬细胞，单核细胞不仅拥有更高水平的先天抵抗因子 APOBEC3G，而且我们还发现以前与抗 HIV 活性无关的 APOBEC3A 在单核细胞抵抗中至关重要。 APOBEC3A 沉默与易感性呈负相关，使单核细胞更容易感染 HIV-1。单核细胞、巨噬细胞和 DC 混杂的差异至少部分可以通过 APOBEC 表达的差异来定义，这对于增强细胞对 HIV-1 的防御具有影响。