Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Viruses. 2020 Sep 25;12(10):1077. doi: 10.3390/v12101077.
Most myeloid lineage cells express the receptor and coreceptors that make them susceptible to infection by primate lentiviruses (SIVs and HIVs). However, macrophages are the only myeloid lineage cell commonly infected by SIVs and/or HIVs. The frequency of infected macrophages varies greatly across specific host and virus combinations as well as disease states, with infection rates being greatest in pathogenic SIV infections of non-natural hosts (i.e., Asian nonhuman primates (Asian NHPs)) and late in untreated HIV-1 infection. In contrast, macrophages from natural SIV hosts (i.e., African NHPs) are largely resistant to infection due to entry and/or post-entry restriction mechanisms. These highly variable rates of macrophage infection may stem from differences in the host immune environment, entry and post-entry restriction mechanisms, the ability of a virus to adapt to efficiently infect macrophages, and the pleiotropic effects of macrophage-tropism including the ability to infect cells lacking CD4 and increased neutralization sensitivity. Questions remain about the relationship between rates of macrophage infection and viral pathogenesis, with some evidence suggesting that elevated levels of macrophage infection may contribute to greater pathogenesis in non-natural SIV hosts. Alternatively, extensive infection of macrophages may only emerge in the context of high viral loads and immunodeficiency, making it a symptom of highly pathogenic infections, not a primary driver of pathogenesis.
大多数髓系细胞表达受体和辅助受体，使它们易受灵长类慢病毒（SIV 和 HIV）感染。然而，巨噬细胞是唯一普遍被 SIV 和/或 HIV 感染的髓系细胞。受感染的巨噬细胞的频率在特定的宿主和病毒组合以及疾病状态下有很大的差异，在非天然宿主（即亚洲非人灵长类动物（亚洲 NHPs））的致病性 SIV 感染和未经治疗的 HIV-1 感染的晚期，感染率最高。相比之下，由于进入和/或进入后限制机制，来自天然 SIV 宿主（即非洲 NHPs）的巨噬细胞基本上不受感染。这些巨噬细胞感染率的高度可变可能源于宿主免疫环境、进入和进入后限制机制、病毒适应有效感染巨噬细胞的能力以及巨噬细胞嗜性的多效性效应（包括感染缺乏 CD4 的细胞和增加中和敏感性的能力）的差异。关于巨噬细胞感染率与病毒发病机制之间的关系仍存在疑问，一些证据表明，巨噬细胞感染水平的升高可能导致非天然 SIV 宿主的发病机制更大。或者，巨噬细胞的广泛感染可能仅在高病毒载量和免疫缺陷的情况下出现，使其成为高度致病性感染的症状，而不是发病机制的主要驱动因素。
