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影响对传染病的敏感性及其临床表现。这些相互作用介导炎性细胞的运输和病毒相关的免疫反应。在病毒感染的情况下，人类CC趋化因子5型受体（CCR5）由于其作为HIV-1协同受体的作用而受到了科学界的高度重视。遗传变异CCR5Δ32（CCR5中的32个碱基对缺失基因）损害细胞表面CCR5的表达，并与纯合子个体预防HIV感染有关。而且，遗传变体CCR5Δ32在诸如炎症和传染病的各种条件下修饰CCR5介导的炎症反应。CCR5拮抗剂至少部分模拟了CCR5Δ32在人类中的自然作用，这解释了人们越来越关注使用CCR5调节剂治疗不同疾病的潜在益处。然而，除了HIV感染外，了解CCR5Δ32变异体在多种病毒感染中的作用对于从更广阔的角度阐明CCR5调节剂的潜在作用至关重要。在这种情况下，这篇综述讨论了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，本次审查解决了CCR5基因编辑和CCR5对健康和病毒性疾病的调控。同样，本文将有关细胞外囊泡（例如外泌体），病毒和CCR5的最新发现联系起来。简要介绍了“ CCR5研究”中被忽略和新兴的主题，重点是Rocio病毒，Zika病毒，Epstein-Barr病毒和Rhino病毒。最后，讨论了CCR5对冠状病毒免疫应答的潜在影响。