CCR5Δ32 mutation and HIV infection: basis for curative HIV therapy

• Homozygous CCR5Δ32/Δ32 mutation renders cells deficient of CCR5 surface expression.
• Naturally CCR5-deficient immune cells are resistant to infection with CCR5-tropic HIV.
• Allogeneic transplantation of CCR5-deficient stem cells have cured a patient of HIV.
• Novel gene editing methods that aim to mimic natural CCR5 deficiency are promising.
• Further development is required to enable curative HIV therapy.

The C–C chemokine receptor 5 (CCR5) is expressed on potential human immunodeficiency virus (HIV) target cells and serves as the predominant co-receptor for viral entry during initial transmission and through the early stages of infection. A homozygous Δ32 mutation in the CCR5 gene prevents CCR5 cell surface expression and thus confers resistance to infection with CCR5-tropic HIV strains. Transplantation of hematopoietic stem cells from a CCR5Δ32/Δ32 donor was previously successful in eliminating HIV from the recipient's immune system, suggesting that targeted CCR5 disruption can lead to an HIV cure. Therefore, intense work is currently being carried out on CCR5 gene-editing tools to develop curative HIV therapy. Here, we review the natural function of CCR5, the progress made on CCR5 gene editing to date and discuss the current limitations.