艾滋病毒的免疫控制。

Muthukumar Balasubramaniam, Jui Pandhare, Chandravanu Dash
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引用次数: 0

摘要

人类免疫缺陷病毒(HIV)感染了表达分化 4 簇细胞表面糖蛋白的免疫细胞(CD4+细胞),导致免疫系统逐渐衰退,引发获得性免疫缺陷综合症(艾滋病)。全球艾滋病毒/艾滋病的持续流行已经夺走了 3500 多万人的生命。即使在疫情流行 37 年后的今天,3,700 万艾滋病病毒感染者(PLHIV)仍无法治愈,也没有发现疫苗来避免每年新增的数百万艾滋病病毒感染者。如果不及时治疗,艾滋病毒感染通常会发展为艾滋病,并最终导致大多数艾滋病毒感染者死亡。推荐的抗逆转录病毒联合疗法(cART)可抑制病毒复制和病毒血症,预防或延缓艾滋病的发展,降低传播率,并降低与艾滋病毒相关的死亡率和发病率。然而,由于 cART 并不能消除 HIV,而且受感染的静息记忆 CD4+ T 细胞(潜伏 HIV 储库)很早就已建立,因此任何 cART 中断都会导致病毒血症复发和疾病进展。因此,要控制艾滋病毒感染,PLHIV 必须严格遵守终生 cART 方案。表达 CD8 糖蛋白的 HIV-1 特异性细胞毒性 T 细胞(CD8+ CTL)通过识别感染细胞表面由人类白细胞抗原(HLA)I 类分子呈现的病毒抗原并杀死这些细胞,从而限制病毒在体内的复制。然而,在没有 cART 的情况下,CTL 无法持久地控制 HIV-1 复制和疾病进展。耐人寻味的是,HIV 控制者(HCs)表现出了在没有 cART 的情况下定义 HIV-1 "功能性治愈 "结果的核心特征:持久的病毒抑制至检测限以下、长期不发展为艾滋病以及没有病毒传播。强大的 HIV-1 特异性 CTL 反应和与持久控制 HIV-1 相关的保护性 HLA 等位基因的流行与 HC 表型有关。了解携带特异性保护性 HLA 等位基因的 HC 中 CTL 介导的抑制 HIV-1 复制和疾病进展的分子机制,可能会为推进 HIV 治愈和预防性 HIV 疫苗的研究提供有前景的见解。
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Immune Control of HIV.

The human immunodeficiency virus (HIV) infection of the immune cells expressing the cluster of differentiation 4 cell surface glycoprotein (CD4+ cells) causes progressive decline of the immune system and leads to the acquired immunodeficiency syndrome (AIDS). The ongoing global HIV/AIDS pandemic has already claimed over 35 million lives. Even after 37 years into the epidemic, neither a cure is available for the 37 million people living with HIV (PLHIV) nor is a vaccine discovered to avert the millions of new HIV infections that continue to occur each year. If left untreated, HIV infection typically progresses to AIDS and, ultimately, causes death in a majority of PLHIV. The recommended combination antiretroviral therapy (cART) suppresses virus replication and viremia, prevents or delays progression to AIDS, reduces transmission rates, and lowers HIV-associated mortality and morbidity. However, because cART does not eliminate HIV, and an enduring pool of infected resting memory CD4+ T cells (latent HIV reservoir) is established early on, any interruption to cART leads to a relapse of viremia and disease progression. Hence, strict adherence to a life-long cART regimen is mandatory for managing HIV infection in PLHIV. The HIV-1-specific cytotoxic T cells expressing the CD8 glycoprotein (CD8+ CTL) limit the virus replication in vivo by recognizing the viral antigens presented by human leukocyte antigen (HLA) class I molecules on the infected cell surface and killing those cells. Nevertheless, CTLs fail to durably control HIV-1 replication and disease progression in the absence of cART. Intriguingly, <1% of cART-naive HIV-infected individuals called elite controllers/HIV controllers (HCs) exhibit the core features that define a HIV-1 "functional cure" outcome in the absence of cART: durable viral suppression to below the limit of detection, long-term non-progression to AIDS, and absence of viral transmission. Robust HIV-1-specific CTL responses and prevalence of protective HLA alleles associated with enduring HIV-1 control have been linked to the HC phenotype. An understanding of the molecular mechanisms underlying the CTL-mediated suppression of HIV-1 replication and disease progression in HCs carrying specific protective HLA alleles may yield promising insights towards advancing the research on HIV cure and prophylactic HIV vaccine.

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