Copy Number Variation of Fc Gamma Receptor Genes in HIV-Infected and HIV-Tuberculosis Co-Infected Individuals in Sub-Saharan Africa

Lee R Machado,Getnet Yimer,Wondwossen Amogne,Maria Viskaduraki,Getachew Aderaye,Jennifer Bowdrey,Ferdinand Mugusi,Omary Minzi,Sabina Mugusi,Abiy Habtewold,Edward J Hollox,Mohammed Janabi,Eyasu Makonnen,Eliford Ngaimisi,Eleni Aklillu

doi:10.1371/journal.pone.0078165

Abstract

AIDS, caused by the retrovirus HIV, remains the largest cause of morbidity in sub-Saharan Africa yet almost all genetic studies have focused on cohorts from Western countries. HIV shows high co-morbidity with tuberculosis (TB), as HIV stimulates the reactivation of latent tuberculosis (TB). Recent clinical trials suggest that an effective anti-HIV response correlates with non-neutralising antibodies. Given that Fcγ receptors are critical in mediating the non-neutralising effects of antibodies, analysis of the extensive variation at Fcγ receptor genes is important. Single nucleotide variation and copy number variation (CNV) of Fcγ receptor genes affects the expression profile, activatory/inhibitory balance, and IgG affinity of the Fcγ receptor repertoire of each individual. In this study we investigated whether CNV of FCGR2C, FCGR3A and FCGR3B as well as the HNA1 allotype of FCGR3B is associated with HIV load, response to highly-active antiretroviral therapy (HAART) and co-infection with TB. We confirmed an effect of TB-co-infection status on HIV load and response to HAART, but no conclusive effect of the genetic variants we tested. We observed a small effect, in Ethiopians, of FCGR3B copy number, where deletion was more frequent in HIV-TB co-infected patients than those infected with HIV alone.

Highlights

AIDS, caused by the T-lymphotropic retrovirus HIV, remains the largest cause of morbidity in sub-Saharan Africa [1]
In the recent RV144 trial, when looking for correlates of protection from HIV-1 infection, it was found that neutralising antibodies and cytotoxic T lymphocyte (CTL) responses were absent in protected patients [8]
In this study we investigated whether copy number variation of FCGR2C, FCGR3A and FCGR3B as well as HNA1 allelic variation of FCGR3B is associated with HIV load, response to highly-active antiretroviral therapy (HAART) and co-infection with TB in two African populations

Summary

Introduction

AIDS, caused by the T-lymphotropic retrovirus HIV, remains the largest cause of morbidity in sub-Saharan Africa [1]. Both genes exhibit copy number variation, deletion of the FCGR3B gene is associated with both SLE and RA, and is likely to cause ectopic expression of the FCGR2B inhibitory receptor on NK cells [19,20].

Results

Conclusion