Gene variant in people of African ancestry influences HIV replication

A genetic variant found in people of African ancestry may help explain naturally occurring lower viral loads of HIV-1.

The variant was discovered by an international team of researchers investigating the high genetic diversity and varying impacts of HIV in Africa. A genome wide association study (GWAS) was performed, where the DNA from nearly 4000 people of African descent with HIV-1 was analysed. The variant, which is found in up to 13 percent of people of African descent, was identified in the CHD1L gene within a region of chromosome 1. The CHD1L gene encodes a DNA repair helicase and limits the replication of HIV in certain white blood cells, acting as a natural defence against HIV.

'By studying a large sample of people of African ancestry, we've been able to identify a new genetic variant that only exists in this population and which is linked to lower HIV viral loads' said Dr Paul McLaren, of the Public Health Agency of Canada, Canada's National Microbiology Laboratory and first author of the paper published in Nature.

In experiments validating the GWAS, scientists at the University of Cambridge's Department of Medicine generated various immune cells derived from induced pluripotent stem cells with CHD1-L altered. After the cells were infected with HIV-1, they discovered that HIV-1 replication was increased in macrophages with CHD1L switched off. However, there was no change observed in T cells.

Dr Harriet Groom, who co-led this research at the University of Cambridge said: 'This gene seems to be important to controlling viral load in people of African ancestry. Although we don't yet know how it's doing this... The link between HIV replication in macrophages and viral load is particularly interesting and unexpected.

This is the first new genetic variant affecting HIV infection identified in nearly 30 years. It is hoped that a better understanding of this gene could improve treatment options for people living with HIV. Although, the researchers have acknowledged that further studies are necessary to investigate if a similar impact is seen in vivo.

The study has been highlighted for increasing representation of African ancestries in human genomic studies, which have been historically underrepresented in the sector.

Professor Manjinder Sandhu, chair in population health and data science in the School of Public Health at Imperial College, and co-senior author, said 'With more than a million new HIV infections a year, it's clear that we still have a long way to go in the fight against HIV. The next step is to fully understand how this genetic variant controls HIV replication'.