Cluster of differentiation 4 (CD4), C-C chemokine receptor type 5 (CCR5), and C-X-C chemokine receptor type 4 (CXCR4) (CD4/CCR5/CXCR4)

The cell-surface entry receptors for the lentiviral envelope, specifically those of the Human Immunodeficiency Virus type 1 (HIV-1), comprise the primary receptor CD4 and the co-receptors CCR5 or CXCR4 (Source: NIH, PubMed). CD4, a member of the immunoglobulin superfamily, is expressed on the surface of T helper cells, monocytes, and macrophages, where it serves as the initial binding site for the viral gp120 glycoprotein (Source: UniProt). This interaction induces conformational changes in gp120, facilitating its subsequent binding to a co-receptor—either CCR5 (a C-C chemokine receptor) or CXCR4 (a C-X-C chemokine receptor), both of which are G protein-coupled receptors (Source: PubMed). These sequential binding events lead to the fusion of the viral and host cell membranes, mediated by the gp41 subunit, allowing the viral core to enter the cytoplasm (Source: Nature Reviews Microbiology). In the context of gene therapy, lentiviral vectors are often pseudotyped with the Vesicular Stomatitis Virus G protein (VSV-G), which utilizes the Low-Density Lipoprotein Receptor (LDLR) for entry, providing a broad cellular tropism (Source: PNAS). Therapeutic agents such as the CCR5 antagonist maraviroc and the CD4-directed antibody ibalizumab target these receptors to block HIV-1 entry and manage infection (Source: FDA). Other agents like plerixafor target CXCR4, although primarily for stem cell mobilization rather than antiviral therapy (Source: PubChem). Understanding these receptors is crucial for developing entry inhibitors and optimizing viral vector delivery in clinical applications.

Other names

HIV-1 entry receptorsLentivirus entry receptorsHIV receptorsCD4/CCR5/CXCR4 complex

Antagonism of the CCR5 or CXCR4 co-receptors to prevent gp120 binding and membrane fusion, and monoclonal antibody binding to CD4 to inhibit post-attachment conformational changes required for viral entry.