What roles do the CD4 receptor, CCR5, and CXCR4 play in HIV infection?

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Diagram illustrating the process of retrovirus infection and reverse transcription, showing a retrovirus entering a host cell, releasing viral RNA, reverse transcriptase converting RNA to DNA, integration into the host genome, transcription of new viral RNA, assembly of new virions, and budding from the cell. — Reverse transcriptase After a retrovirus infects a cell, an enzyme known as reverse transcriptase converts viral RNA into proviral DNA in the cytoplasm. Proviral DNA then enters the nucleus, where it is incorporated into the host cell's DNA.

In the context of HIV infection, the CD4 receptor and chemokine receptors CCR5 and CXCR4 function as essential entry points for the virus into host helper T cells.1

CD4 Receptor: The viral envelope protein gp120 first binds to the CD4 molecule on the surface of the helper T cell. This initial attachment triggers a series of reactions that prepare the virus for entry.1
CCR5 and CXCR4: These proteins act as coreceptors. Once gp120 binds to CD4, it undergoes a conformational change that allows it to interact with either CCR5 or CXCR4. This interaction triggers a further change in the viral protein gp41, which facilitates the fusion of the viral envelope with the host cell membrane, allowing the viral genetic material to enter the cell.1

Once inside, the virus utilizes the enzyme reverse transcriptase to convert its RNA into DNA, enabling it to integrate into the host genome. Because these receptors are critical for entry, they are significant targets for antiretroviral drug development.1