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CCR5-Δ32等位基因纯合个体中的HIV-1感染:下一个病例及综述

HIV-1 Infection in Persons Homozygous for CCR5-Δ32 Allele: The Next Case and the Review.

作者信息

Smoleń-Dzirba Joanna, Rosińska Magdalena, Janiec Janusz, Beniowski Marek, Cycoń Mariusz, Bratosiewicz-Wąsik Jolanta, Wąsik Tomasz J

机构信息

Department of Microbiology and Virology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Poland.

Department of Epidemiology, National Institute of Public Health - National Institute of Hygiene, Warsaw, Poland.

出版信息

AIDS Rev. 2017 Dec;19(4):219-230.

Abstract

CC-chemokine receptor 5 serves as the coreceptor for the HIV-1 R5 strains, which are responsible for the majority of HIV transmissions. A deletion of 32 nucleotides in the gene encoding this receptor (termed CCR5-Δ32) leads to the suppression of CC-chemokine receptor 5 presentation at the cell surface, thus impeding process of HIV entry into the cell. Individuals homozygous for the CCR5-Δ32 allele are resistant to infection with HIV-1 R5 strains, and are extremely rare among HIV-1-infected individuals. We have described a case of person homozygous for CCR5-Δ32, who was infected with subtype B HIV-1. Based on examination of proviral V3 sequences obtained from the first clinical blood sample within less than five months after seroconversion, the CXC-chemokine receptor 4-using strains (X4 or R5/X4) were detected. Data on HIV-1-infected patients homozygous for the CCR5-Δ32 allele, course of HIV-1 infection in these cases, and the infecting viral strains from current and all former reports on HIV-1 infection in CCR5-Δ32 homozygotes were gathered and compared. Identification of HIV-1-infected persons homozygous for CCR5-Δ32 supports the evidence that the lack of functional CC-chemokine receptor 5 at the cell surface does not confer absolute protection against HIV-1 infection, which should be considered when designing future HIV pre-exposure prophylaxis schemes basing on CC-chemokine receptor 5 blocking drugs.

摘要

CC趋化因子受体5作为HIV-1 R5毒株的共受体,而这些毒株导致了大多数的HIV传播。编码该受体的基因中32个核苷酸的缺失(称为CCR5-Δ32)会导致CC趋化因子受体5在细胞表面的表达受到抑制,从而阻碍HIV进入细胞的过程。CCR5-Δ32等位基因纯合的个体对HIV-1 R5毒株感染具有抗性,并且在HIV-1感染个体中极为罕见。我们描述了一例CCR5-Δ32纯合的个体,其感染了B亚型HIV-1。基于对血清转化后不到五个月内从首次临床血样中获得的前病毒V3序列的检测,发现了使用CXC趋化因子受体4的毒株(X4或R5/X4)。收集并比较了关于CCR5-Δ32等位基因纯合的HIV-1感染患者的数据、这些病例中HIV-1感染的病程以及来自目前和所有既往关于CCR5-Δ32纯合子中HIV-1感染报告的感染病毒株。鉴定出CCR5-Δ32纯合的HIV-1感染个体支持了以下证据:细胞表面缺乏功能性CC趋化因子受体5并不能提供针对HIV-1感染的绝对保护,在设计未来基于CC趋化因子受体5阻断药物的HIV暴露前预防方案时应考虑这一点。

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