Africa-specific human genetic variation near CHD1L associates with HIV-1 load. Nature
McLaren et al. assessed genetic factors that determine HIV-1 viral replication capacity among individuals of African descent.
The authors performed a genome-wide association study including more than 3’800 individuals from the International Collaboration for the Genomics of HIV. This collaboration included individuals from 11 cohorts, with the majority being African American, and a minority of individuals being from Kenya. The authors assessed around 10 million common genetic variants for association with the set-point HIV viral load, an established correlate for disease progression and transmission potential. In addition, in-vitro experiments were performed to evaluate the biological plausibility of their findings.
In addition to a region on the HLA-B gene which was previously identified to be associated with HIV control, the authors identified a new locus on chromosome 1 (CHD1L), which seems to be specific for individuals of African ancestry. The presence of the genetic variant conferred a reduction in the set-point viral load of 0.17-0.57 log10-transformed RNA copies per mL. The observed reduction is of similar magnitude to the one conferred by the CCR5Δ32 allele, which slows disease progression in heterozygote individuals and leads to HIV-resistance in homozygote individuals of European ancestries. CHD1L encodes for a protein involved in DNA repair, and interacts with an enzyme implicated in HIV-1 integration and transcription. Knock-out of CHD1L in in-vitro HIV-1 infection models led to increased viral replication, confirming that CHD1L is implicated in HIV replication.
Taken together, the present study provides strong evidence that variants in the CHD1L gene limit HIV-1 viral replication. These variants seem to be specific to individuals of African descent, highlighting the need for dedicated studies in this often under-represented patient population. Future studies aimed at understanding the mechanisms behind the observed association may inform new treatment options for people with HIV worldwide.