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Review
. 2024 Jan 23;21(1):2.
doi: 10.1186/s12977-024-00634-1.

The chemokine receptor CCR5: multi-faceted hook for HIV-1

Natacha Faivre  1   2   3 , Christel Verollet  1   2   3 , Fabrice Dumas  4
Affiliations
Review

The chemokine receptor CCR5: multi-faceted hook for HIV-1

Natacha Faivre et al. Retrovirology. .

Abstract

Chemokines are cytokines whose primary role is cellular activation and stimulation of leukocyte migration. They perform their various functions by interacting with G protein-coupled cell surface receptors (GPCRs) and are involved in the regulation of many biological processes such as apoptosis, proliferation, angiogenesis, hematopoiesis or organogenesis. They contribute to the maintenance of the homeostasis of lymphocytes and coordinate the function of the immune system. However, chemokines and their receptors are sometimes hijacked by some pathogens to infect the host organism. For a given chemokine receptor, there is a wide structural, organizational and conformational diversity. In this review, we describe the evidence for structural variety reported for the chemokine receptor CCR5, how this variability can be exploited by HIV-1 to infect its target cells and what therapeutic solutions are currently being developed to overcome this problem.

Keywords: CCR5; Chemokine receptor; Conformation; HIV-1; Lipid membrane.

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Conflict of interest statement

The authors declare no scientific, commercial or financial competing interests.

Figures

Fig. 1
Fig. 1
Schematic view of the early steps of HIV infection. The HIV envelope (Env), consisting of gp120 and gp41 subunits, first binds to the CD4 receptor located at the plasma membrane of the infected cell (1). This binding induces a conformational change in gp120 that allows the interaction of its V3 loop with a co-receptor (2). The co-receptor can be either CCR5 or CXCR4, defining the tropism of the virus (see main text). This second binding induces a new conformational change in gp120 which exposes the fusion peptide of gp41 that anchors its N-terminal domain into the plasma membrane of the target cell (3). This initiates a process of fusion that will lead to the release of the viral content into the cytoplasm of the infected cell (for more details see [38, 54])
Fig. 2
Fig. 2
Schematic representation of the factors that can influence the 3D-structure of CCR5 coreceptor. A Post-translational modifications (PMTs): sites of O-Glycosylation (Ser6, Thr16, Ser17) [70, 71], sulfation (Tyr3, 10, 14, 15) [, –78], palmitoylation (Cys321, 323 and 324) [–91] and phosphorylation (Ser336, 337, 342 and 349) [235, 236] are represented by colored circles. Factors such as G-protein coupling (B) [, , –103], mutations (C) [–129, 177, 178], surface density [–123] and oligomerization [–149] (D) and membrane surrounding [–173] (E) are also exemplified
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