Association Among CCR5 Genotypes, CCR5 Expression, And In Vitro HIV Infection

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.

Name thesis:degree_name

Master of Sciences

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Biology

Grantor dc:publisher

Case Western Reserve University School of Graduate Studies

Year dc:date

2013

Author dc:creator

• John, Bangan

Contributors dc:contributor

• Zimmerman, Peter

• Biology
• Biomedical Research
• Cellular Biology
• Genetics
• Health Sciences
• Immunology
• HIV infection
• CCR5
• genotypes
• gene polymorphisms
• antiretroviral therapy
• Papua New Guinea

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=case1365888090

OAI identifier oai:identifier

oai:etd.ohiolink.edu:case1365888090