Host genetic variation at a locus near CHD1L impacts HIV sequence diversity in a South African population

Abstract

ABSTRACT There is variability in viral load (VL) among individuals with untreated human immunodeficiency virus (HIV) infection, and this variability can be partly attributed to host genetics. HIV is known to develop escape mutations to evade host immune pressure, particularly from HLA alleles and, in some cases, counteracts the protective effect of host alleles. A recent genome-wide association study (GWAS) of HIV VL in individuals of African ancestry identified a locus on chromosome 1, near the protein-coding gene chromodomain helicase DNA-binding protein 1 like ( CHD1L ), that has a novel association with control of HIV replication. However, not all individuals carrying the protective alleles maintain low VL, and the region’s impact on viral evolution has not been investigated. To address this, we conducted a host-virus regional association analysis in 147 people living with HIV (PLWH) from South Africa with both human and viral genome data available. We observed significant associations between the CHD1L variants rs77029719 (G) ( P = 1.6 × 10 −2 ), rs7519713 (T) ( P = 2.3 × 10 −2 ), and rs59784663 (G) and 73004025 (T) ( P = 1.4 × 10 −2 ) with codon 248 of HIV reverse transcriptase (RT) and between CHD1L variant rs7519713 (T) and codon 18 ( P = 3.2 × 10 −2 ) and 147 ( P = 3.9 × 10 −2 ) of HIV gag. These associations are consistent with viral escape from CHD1L pressure. In addition, we observed significant associations between HLA B*81 ( P = 1.5 × 10 −5 ) and HLA C*18 ( P = 7.0 × 10 −4 ) with RT codon 4 and HLAB*58 with RT codon 196 ( P = 9.0 × 10 −4 ). This study reveals new evidence of host genetic variation impacting viral evolution in a population highly affected by HIV. IMPORTANCE It has been previously shown that genetic variants near CHD1L on chromosome 1 are associated with reduced HIV VL in African populations. However, the impact of these variants on viral diversity and how they restrict viral replication are unknown. We report on a regional association analysis in a South African population and show evidence of selective pressure by variants near CHD1L on HIV RT and gag. Our findings provide further insight into how genetic variability at this locus contributes to host control of HIV in a South African population.