Open Access Open Badges Research

The role of G protein gene GNB3 C825T Polymorphism in HIV-1 acquisition, progression and immune activation

Jennifer Juno1, Jeffrey Tuff2, Robert Choi3, Catherine Card1, Joshua Kimani145, Charles Wachihi4, Sandra Koesters-Kiazyk2, T Blake Ball1256, Carey Farquhar789, Francis A Plummer1102, Grace John-Stewart789, Ma Luo12 and Keith R Fowke1105*

Author Affiliations

1 Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada

2 National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Canada

3 Department of Medicine, University of Washington, Seattle USA

4 Kenya AIDS Control Program, Nairobi, Kenya

5 Department of Medical Microbiology, University of Nairobi, Nairobi Kenya

6 Department of Immunology, University of Manitoba, Winnipeg, Canada

7 Department of Medicine, University of Washington, Seattle, USA

8 Department of Epidemiology, University of Washington, Seattle, USA

9 Department Global Health, University of Washington, Seattle USA

10 Departments of Community Health Sciences University of Manitoba, Winnipeg Canada

For all author emails, please log on.

Retrovirology 2012, 9:1  doi:10.1186/1742-4690-9-1

Published: 3 January 2012



The GNB3 C825T polymorphism is associated with increased G protein-mediated signal transduction, SDF-1α-mediated lymphocyte chemotaxis, accelerated HIV-1 progression, and altered responses to antiretroviral therapy among Caucasian subjects. The GNB3 825T allele is highly prevalent in African populations, and as such any impact on HIV-1 acquisition or progression rates could have a dramatic impact. This study examines the association of the 825T polymorphism with HIV-1 acquisition, disease progression and immune activation in two African cohorts. GNB3 825 genotyping was performed for enrolees in both a commercial sex worker cohort and a perinatal HIV transmission (PHT) cohort in Nairobi, Kenya. Ex vivo immune activation was quantified by flow cytometry, and plasma chemokine levels were assessed by cytokine bead array.


GNB3 genotype was not associated with sexual or vertical HIV-1 acquisition within these cohorts. Within the Pumwani cohort, GNB3 genotype did not affect HIV-1 disease progression among seroconverters or among HIV-1-positive individuals after adjustment for baseline CD4 count. Maternal CD4 decline and viral load increase in the PHT cohort did not differ between genotypes. Multi-parametric flow cytometry assessment of T cell activation (CD69, HLA-DR, CD38) and Treg frequency (CD25+FOXP3+) found no differences between genotype groups. Plasma SDF-1α, MIP-1β and TRAIL levels quantified by cytokine bead array were also similar between groups.


In contrast to previous reports, we were unable to provide evidence to suggest that the GNB3 C825T polymorphism affects HIV-1 acquisition or disease progression within African populations. Ex vivo immune activation and plasma chemokine levels were similarly unaffected by GNB3 genotype in both HIV-1-negative and HIV-1-positive individuals. The paucity of studies investigating the impact of GNB3 polymorphism among African populations and the lack of mechanistic studies make it difficult to assess the true biological significance of this polymorphism in HIV-1 infection.

GNB3; HIV progression; G protein; HIV acquisition; Immune Activation