Telenti Amalio
Institute of Microbiology, University Hospital Center, University of Lausanne, Lausanne, Switzerland.
Curr Opin HIV AIDS. 2009 Mar;4(2):131-5. doi: 10.1097/COH.0b013e3283223d76.
Clinical trials of CCR5 antagonists attest to their efficacy and tolerance in HIV treatment. However, there has been debate on their long-term safety because of the role of CCR5 in innate immunity. This review highlights gaps in our understanding of epidemiology of infections that are modulated by CCR5, in particular, in HIV-infected individuals.
In the mouse model, CCR5 has a role in the response against pathogens as diverse as Toxoplama gondii, West Nile virus, Mycobacterium tuberculosis, herpes simplex virus, Trypanosoma cruzi, Cryptococcus neoformans, Chlamydia trachomatis, Listeria, and plasmodia. In human cohorts, individuals carrying the defective CCR5Delta32 allele present an increased susceptibility to flavivirus (West Nile virus and tickborne encephalitis virus). The selective pressures that led to the spread of loss-of-function CCR5 mutations in humans (CCR5Delta32), and in mangabeys (CCR5Delta24) are not understood.
The recent availability of CCR5 antagonists has raised concern that genetic, biological, or chemical CCR5 knockout, although beneficial against some pathogens (i.e. HIV), could be deleterious for other processes implicated in pathogen response. The consequences of long-term pharmaceutical intervention on CCR5 should be carefully assessed through rigorous postmarketing surveillance.
CCR5拮抗剂的临床试验证明了其在HIV治疗中的疗效和耐受性。然而，由于CCR5在天然免疫中的作用，关于其长期安全性一直存在争议。本综述强调了我们在理解由CCR5调节的感染流行病学方面的差距，特别是在HIV感染者中。
在小鼠模型中，CCR5在对抗多种病原体的反应中发挥作用，这些病原体包括刚地弓形虫、西尼罗河病毒、结核分枝杆菌、单纯疱疹病毒、克氏锥虫、新型隐球菌、沙眼衣原体、李斯特菌和疟原虫。在人类队列中，携带缺陷型CCR5Δ32等位基因的个体对黄病毒（西尼罗河病毒和蜱传脑炎病毒）的易感性增加。导致人类（CCR5Δ32）和白颈白眉猴（CCR5Δ24）中功能丧失型CCR5突变传播的选择压力尚不清楚。
CCR5拮抗剂的近期出现引发了人们的担忧，即基因、生物或化学方法敲除CCR5，虽然对某些病原体（如HIV）有益，但可能对参与病原体反应的其他过程有害。应通过严格的上市后监测仔细评估长期药物干预对CCR5的影响。
