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Chemokine receptor allelic polymorphisms: relationships to HIV resistance and disease progression
1Department of Human Retrovirology, Academic Medical Center, Meibergdreef 15, Amsterdam, 1105 AZ, The Netherlands.
Abstract:
It is now well established that an array of CC and CXC chemokine receptors, in association with the CD4 molecule, can interact with the HIV-1 gp120 protein to facilitate viral fusion. A 32bp deletion in the CC chemokine receptor CCR5, the major M-tropic viral co-receptor, provides considerable protection against HIV-1 transmission and has been associated with a delay in disease progression. The effects of the Delta32 allele appear to be mediated through the phenotype of CCR5 expression as opposed to genotype. Here we discuss the potential effects that the Delta32 allele and other polymorphisms in the chemokine receptor repertoire may have on both HIV-1 transmission and disease progression.
Insights
A CCR5 gene deletion (Delta32 allele) offers protection against HIV-1 transmission and delays disease progression. This effect is linked to CCR5 receptor expression levels, not just the genetic makeup.
Area of Science:
- Immunology
- Virology
- Genetics
Background:
- Chemokine receptors (CC and CXC) and CD4 interact with HIV-1 gp120, facilitating viral fusion.
- A specific deletion (32bp) in the CCR5 receptor gene (Delta32 allele) is linked to protection against HIV-1.
- This CCR5 Delta32 allele is associated with delayed HIV-1 disease progression.
Purpose of the Study:
- To discuss the impact of the CCR5 Delta32 allele on HIV-1 transmission and disease.
- To explore how CCR5 expression phenotypes, rather than genotypes, mediate the Delta32 allele's effects.
- To examine the potential influence of other chemokine receptor polymorphisms on HIV-1 outcomes.
Main Methods:
- Review of existing literature on chemokine receptors and HIV-1.
- Analysis of the role of CCR5 and its Delta32 allele in HIV-1 infection.
- Discussion of genotype versus phenotype in relation to CCR5 function.
Main Results:
- The CCR5 Delta32 allele confers significant protection against HIV-1 transmission.
- Individuals with the Delta32 allele often experience delayed progression of HIV-1 disease.
- The protective effects are primarily associated with CCR5 receptor expression levels.
Conclusions:
- CCR5 receptor polymorphisms, particularly the Delta32 allele, are crucial in modulating HIV-1 infection.
- Understanding CCR5 expression is key to comprehending protection against HIV-1.
- Further research into chemokine receptor variations may reveal new therapeutic targets for HIV-1.