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Prog Mol Biol Transl Sci. 2019;161:113-124. doi: 10.1016/bs.pmbts.2018.10.001. Epub 2018 Nov 20.

Mutations in chemokine receptors and AIDS.

Author information

1
International Education College, Henan University, Kaifeng, China.
2
Center for Translational Medicine, Huaihe Clinical College, Huaihe Hospital of Henan University, Kaifeng, China. Electronic address: yqkuang@vip.henu.edu.cn.

Abstract

Chemokines are a class of chemotactic small molecule peptides whose receptors CCR5 and CXCR4 play important role in the entry of human immunodeficiency virus (HIV-1) into immune cells. Chemokines belong to G protein-coupled receptor superfamily containing seven hydrophobic transmembrane helices, causing physiological effects such as chemotaxis, immune regulation, antiviral immunity, regulation of hematopoiesis and angiogenesis, as well as cell growth and metabolism, through certain signaling pathways. Earlier studies have shown that HIV infects the human immune cells by binding to the CD4 receptor. Soon, it was discovered that HIV-1 enters into human immune cells by binding to another receptor, chemokine receptor, which acts as co-receptor for CD4 during the invasion of HIV-1 into cells. Since complex receptor binding is important for HIV-1 invasion, antagonizing the binding has become an attractive and rational drug design goal. Early studies sought to block the interaction between virus and the receptors by chemically modifying the CCR5 and CXCR4 ligands. Although drug treatment is widely used, drug treatment cannot cure AIDS; it can only inhibit the replication of the virus, and HIV/AIDS patients need to take drugs for life. In addition, anti-AIDS drugs also produce side effects such as diseases of the cardiovascular system, nervous system, and metabolic system. In 2006, the emergence of "Berlin patient" led researchers to focus on gene therapy in chemokine receptors. In 2006 and 2007, the attending physician of "Berlin patient" cured his AIDS by transplantation of the stem cells from a donor who was homozygous for the CCR5 Δ32 mutation. This review summarizes the research progress in the mutation in chemokine receptor of HIV/AIDS.

KEYWORDS:

AIDS; CCR5 disruption; CXCR4 disruption; Chemokine receptor; HIV

PMID:
30711024
DOI:
10.1016/bs.pmbts.2018.10.001
[Indexed for MEDLINE]

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