CCR5-Δ32

CCR5-Δ32

The CCR5-Δ32 mutation is a well-studied genetic variant that affects the CCR5 gene, which encodes a protein that acts as a receptor on the surface of white blood cells. This mutation results in a deletion of 32 base pairs in the CCR5 gene, leading to a nonfunctional receptor. The CCR5 receptor is known to play a crucial role in the immune system, particularly in the entry of certain strains of the human immunodeficiency virus (HIV) into host cells.

Genetic Basis

The CCR5-Δ32 mutation is characterized by a 32 base pair deletion in the coding region of the CCR5 gene, located on chromosome 3p21. This deletion results in a frameshift mutation, producing a truncated protein that is not expressed on the cell surface. Individuals who are homozygous for the CCR5-Δ32 mutation (i.e., they have two copies of the mutated gene) are resistant to HIV-1 infection, as the virus cannot enter their cells via the CCR5 receptor.

Epidemiology

The CCR5-Δ32 allele is most commonly found in populations of European descent, with a frequency of about 10% in Northern Europe. The mutation is less common in Southern Europe and is rare in African, Asian, and Native American populations. The high prevalence of the CCR5-Δ32 mutation in European populations has led to speculation about its evolutionary origins, with some hypotheses suggesting that it conferred a survival advantage during past epidemics, such as the bubonic plague or smallpox.

Clinical Significance

The CCR5-Δ32 mutation has significant implications for HIV infection and treatment. Individuals who are homozygous for the mutation are highly resistant to HIV-1, as the virus primarily uses the CCR5 receptor to enter host cells. Heterozygous individuals (those with one copy of the mutation) may experience a slower progression of the disease. This mutation has also been a target for therapeutic interventions, such as the development of CCR5 antagonists that block the receptor and prevent HIV entry.

Research and Therapeutic Applications

Research into the CCR5-Δ32 mutation has led to the development of novel therapeutic strategies for HIV/AIDS. One such approach involves the use of gene editing technologies, such as CRISPR-Cas9, to introduce the CCR5-Δ32 mutation into the genome of patients' immune cells, thereby conferring resistance to HIV. Additionally, CCR5 antagonists, such as maraviroc, have been developed to block the receptor and inhibit viral entry.

Also see

• CCR5 receptor
• HIV/AIDS
• Gene therapy
• CRISPR-Cas9
• Maraviroc