1. Association Among CCR5 Genotypes, CCR5 Expression, And In Vitro HIV Infection
- Author
-
John, Bangan
- Subjects
- Biology, Biomedical Research, Cellular Biology, Genetics, Health Sciences, Immunology, HIV infection, CCR5, genotypes, gene polymorphisms, antiretroviral therapy, Papua New Guinea
- Abstract
The single nucleotide polymorphisms (SNPs) in CCR5 (-2459 G>A [promoter], ¿32 deletion polymorphism [open reading frame, ORF]) influences the expression of CCR5 chemokine receptor on human T lymphocytes. CCR5 is a major coreceptor for HIV to bind to the T cell prior to fusion. Individuals have various frequencies of these polymorphisms, which influence their susceptible to HIV infection and disease progression. This thesis is focused on determining the association between these polymorphisms and CCR5 expression on T cells, as well as between these polymorphisms and in vitro HIV infection. The CCR5 -2459 genotype results that were obtained showed clear associations with CCR5 expression on the central memory T cell (TCM) subpopulation. That is, CCR5 -2459 G/G had lower levels of CCR5 expression as compared to A/A and G/A on the TCM cells. While with the CCR5 ORF genotypes, wildtype (Wt)/¿32 had very low levels of CCR5 expression as compared to Wt/Wt. Furthermore, results obtained for CCR5 -2459 genotype and HIV infectivity of the TCM cells also clearly showed significant associations. These were observed when comparing CCR5 -2459 genotypes G/G and A/A (p=0.029), and also between G/A and G/G (p=0.049). That is, G/G had lower HIV infectivity of its TCM cells in comparison to those of both A/A and G/A genotypes. These findings, especially those of CCR5 -2459 G allele demonstrates its protective effect in the in vitro assay, thus, providing insights into expression and infection at the T cell subpopulation level.
- Published
- 2013