Hendricks Chynna M, Cordeiro Thaissa, Gomes Ana Paula, Stevenson Mario
Department of Microbiology & Immunology, Miller School of Medicine, University of Miami, Miami, FL, United States.
Department of Medicine, Miller School of Medicine, University of Miami, Miami, FL, United States.
Front Microbiol. 2021 Apr 7;12:646447. doi: 10.3389/fmicb.2021.646447. eCollection 2021.
HIV-1 has evolved mechanisms to evade host cell immune responses and persist for lifelong infection. Latent cellular reservoirs are responsible for this persistence of HIV-1 despite the powerful effects of highly active antiretroviral therapies (HAART) to control circulating viral load. While cellular reservoirs have been extensively studied, much of these studies have focused on peripheral blood and resting memory CD4+ T cells containing latent HIV-1 provirus; however, efforts to eradicate cellular reservoirs have been stunted by reservoirs found in tissues compartments that are not easily accessible. These tissues contain resting memory CD4+ T cells and tissue resident macrophages, another latent cellular reservoir to HIV-1. Tissue resident macrophages have been associated with HIV-1 infection since the 1980s, and evidence has continued to grow regarding their role in HIV-1 persistence. Specific biological characteristics play a vital role as to why macrophages are latent cellular reservoirs for HIV-1, and and studies exhibit how macrophages contribute to viral persistence in individuals and animals on antiretroviral therapies. In this review, we characterize the role and evolutionary advantages of macrophage reservoirs to HIV-1 and their contribution to HIV-1 persistence. In acknowledging the interplay of HIV-1 and macrophages in the host, we identify reasons why current strategies are incapable of eliminating HIV-1 reservoirs and why efforts must focus on eradicating reservoirs to find a future functional cure.
人类免疫缺陷病毒1型（HIV-1）已经进化出逃避宿主细胞免疫反应并持续终身感染的机制。尽管高效抗逆转录病毒疗法（HAART）对控制循环病毒载量有强大作用，但潜伏的细胞储存库导致HIV-1持续存在。虽然对细胞储存库进行了广泛研究，但这些研究大多集中在外周血和含有潜伏HIV-1前病毒的静息记忆CD4+T细胞上；然而，由于在不易接近的组织隔室中发现的储存库，根除细胞储存库的努力受到了阻碍。这些组织含有静息记忆CD4+T细胞和组织驻留巨噬细胞，后者是HIV-1的另一个潜伏细胞储存库。自20世纪80年代以来，组织驻留巨噬细胞就与HIV-1感染有关，而且关于它们在HIV-1持续存在中的作用的证据不断增加。特定的生物学特性对于巨噬细胞为何是HIV-1的潜伏细胞储存库起着至关重要的作用，并且研究展示了巨噬细胞如何在接受抗逆转录病毒治疗的个体和动物中促进病毒持续存在。在这篇综述中，我们描述了巨噬细胞储存库对HIV-1的作用、进化优势及其对HIV-1持续存在的贡献。在认识到HIV-1与巨噬细胞在宿主体内的相互作用后，我们确定了当前策略无法消除HIV-1储存库的原因，以及为什么必须集中精力根除储存库以找到未来的功能性治愈方法。
