超越 HIV 感染：CCR5 和 CCR5Δ32 对病毒病的被忽视和多样影响。
Beyond HIV infection: Neglected and varied impacts of CCR5 and CCR5Δ32 on viral diseases.
机构信息
Laboratório de Imunobiologia e Imunogenética, Departamento de Genética, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Brazil; Programa de Pós-Graduação em Genética e Biologia Molecular, Departamento de Genética, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Brazil.
Laboratório de Imunobiologia e Imunogenética, Departamento de Genética, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Brazil; Programa de Pós-Graduação em Genética e Biologia Molecular, Departamento de Genética, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Brazil; Programa de Pós-Graduação em Biotecnologia, Laboratório de Imunologia Aplicada, Instituto de Ciência e Tecnologia - ICT, Universidade Federal de São Paulo - UNIFESP, São José dos Campos, São Paulo, Brazil.
出版信息
Virus Res. 2020 Sep;286:198040. doi: 10.1016/j.virusres.2020.198040. Epub 2020 May 30.
The interactions between chemokine receptors and their ligands may affect susceptibility to infectious diseases as well as their clinical manifestations. These interactions mediate both the traffic of inflammatory cells and virus-associated immune responses. In the context of viral infections, the human C-C chemokine receptor type 5 (CCR5) receives great attention from the scientific community due to its role as an HIV-1 co-receptor. The genetic variant CCR5Δ32 (32 base-pair deletion in CCR5 gene) impairs CCR5 expression on the cell surface and is associated with protection against HIV infection in homozygous individuals. Also, the genetic variant CCR5Δ32 modifies the CCR5-mediated inflammatory responses in various conditions, such as inflammatory and infectious diseases. CCR5 antagonists mimic, at least in part, the natural effects of the CCR5Δ32 in humans, which explains the growing interest in the potential benefits of using CCR5 modulators for the treatment of different diseases. Nevertheless, beyond HIV infection, understanding the effects of the CCR5Δ32 variant in multiple viral infections is essential to shed light on the potential effects of the CCR5 modulators from a broader perspective. In this context, this review discusses the involvement of CCR5 and the effects of the CCR5Δ32 in human infections caused by the following pathogens: West Nile virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus. Subsequently, this review addresses the impacts of CCR5 gene editing and CCR5 modulation on health and viral diseases. Also, this article connects recent findings regarding extracellular vesicles (e.g., exosomes), viruses, and CCR5. Neglected and emerging topics in "CCR5 research" are briefly described, with focus on Rocio virus, Zika virus, Epstein-Barr virus, and Rhinovirus. Finally, the potential influence of CCR5 on the immune responses to coronaviruses is discussed.
趋化因子受体及其配体之间的相互作用可能会影响对传染病的易感性及其临床表现。这些相互作用介导炎症细胞的迁移和与病毒相关的免疫反应。在病毒感染的背景下，人类 C-C 趋化因子受体 5（CCR5）因其作为 HIV-1 共受体的作用而受到科学界的极大关注。CCR5 基因中的 32 个碱基对缺失（CCR5Δ32）的遗传变异会损害细胞表面的 CCR5 表达，并且与纯合个体对 HIV 感染的保护有关。此外，CCR5Δ32 遗传变异还会改变 CCR5 介导的各种情况下的炎症反应，如炎症和传染病。CCR5 拮抗剂至少在一定程度上模拟了 CCR5Δ32 在人类中的自然作用，这解释了人们对使用 CCR5 调节剂治疗不同疾病的潜在益处的日益关注。然而，除了 HIV 感染之外，了解 CCR5Δ32 变异在多种病毒感染中的作用对于从更广泛的角度阐明 CCR5 调节剂的潜在影响至关重要。在这种情况下，本文讨论了 CCR5 的参与以及 CCR5Δ32 在以下病原体引起的人类感染中的作用：西尼罗河病毒、流感病毒、人乳头瘤病毒、乙型肝炎病毒、丙型肝炎病毒、脊髓灰质炎病毒、登革热病毒、人巨细胞病毒、克里米亚-刚果出血热病毒、肠病毒、日本脑炎病毒和汉坦病毒。随后，本文探讨了 CCR5 基因编辑和 CCR5 调节对健康和病毒疾病的影响。此外，本文还将最近关于细胞外囊泡（例如外泌体）、病毒和 CCR5 的发现联系起来。简要描述了“CCR5 研究”中被忽视和新兴的主题，重点介绍了罗西奥病毒、寨卡病毒、爱泼斯坦-巴尔病毒和鼻病毒。最后，讨论了 CCR5 对冠状病毒免疫反应的潜在影响。
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