H3Africa PI: Dr. Mogomotsi Matshaba
Institution: University Of Botswana / IHS-Gaborone
Project Affiliation: CAfGEN
Understanding molecular interactions of viruses and hosts immune system is critical to discovery of novel treatments and improving existing ones. Human APOBEC3G are cytidine deaminases forming part of the innate immune system which mediate against retroviruses such as HIV-1. Most of studies regarding the putative effects of APOBEC 3G on HIV-1 have been done on Caucasian adult populations, even though Sub-Saharan Africa has been disproportionately affected by HIV/AIDS. Botswana and Uganda are some of the countries with a relatively high HIV prevalence, yet there’s little data on HIV-1 host genomics, particularly with regards to children. However, children remain an important cohort since their HIV-1 disease progression is less likely to be influenced by lifestyle behaviors, such as smoking and excessive alcohol drinking, compared to their adult counterparts. This study characterizes genetic variants of the APOBEC3G gene to determine level of variability and association with HIV-1 Rapid Progression/Long Term Non-Progression status. This is a retrospective study analyzing whole exome sequences of perinatally HIV infected paediatrics from Botswana and Uganda. DNA was collected from whole blood using PAXgene Blood DNA kit. Exome sequencing was performed on an Illumina Hiseq 2500 after exome capture with VCRome v2.1 capture kit. Variants were jointly called using the GATK v3.5.0 Haplotype Caller. Sequence variant quality was assessed using VCFTools and SnpEff with a minimum depth of 10x, Phred score >30 and genotype quality score> 20. Variant Tools (v.2.6.1) was used for exon annotation. Statistical analysis, with a statistical significance level of 0.05, is in progress and a few potential variants have been identified.
NEXT STEPS: Further data analysis and variant verification is to continue with an anticipated completion date of September 2023. Thereafter manuscripts writing will commence followed by publications.