A gene that acts as natural defence against HIV has been identified in people of African descent, according to a new international study.
It is the first new genetic variant related to HIV infection discovered in nearly 30 years of research and the team, co-led by Ecole Polytechnique Fédérale de Lausanne (EPFL), France; Canada’s National Microbiology Laboratory; and Imperial College London, hope their discovery will pave the way for new treatment strategies.
Writing in the latest edition of Nature, they describe using a combination of computational and experimental approaches to explore the biological mechanism behind the genetic association, ultimately finding the gene CHD1L acts to limit HIV replication in a subset of white blood cells.
The degree of viral infection is measured by the virus’ “setpoint viral load” (spVL), which refers to the relatively stable level of HIV replication in the body after the initial, acute phase of infection in untreated individuals.
Although there have been large studies of spVL control in populations of European descent, much less has been done in populations of African.
To address this disparity, a large international collaboration of scientists and clinicians completed a large-scale genome-wide association study (GWAS), using data from diverse populations of African ancestries.
They analysed the genomes from 3,879 individuals living with HIV-1 and used computational analysis and fine-mapping techniques to identify a novel region in the genome that shows a strong association with spVL control.
This region corresponds to the CHD1L gene, which encodes a protein that helps DNA unwind after it has been damaged, allowing it to be repaired.
But in this study, the CHD1L gene showed genetic variation specific to populations of African ancestries, and that was linked to the spontaneous control of HIV-1, the most common and virulent type of HIV.
The discovery of CHD1L’s role in limiting HIV replication could lead to improved treatment options for infected individuals
Study co-leader Professor Jacques Fellay, of EPFL’s School of Life Sciences, said: “Our findings provide insights into potential therapeutic targets, which are needed to continue the fight against HIV-1.
“In addition, our results underscore the importance of performing genomic studies in diverse ancestral populations to better address their specific medical needs and global health inequities.”
Co-author Professor Manjinder Sandhu, from the Faculty of Medicine at Imperial College London, added: “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 – we are yet to have a vaccine to prevent infection, have yet to find a cure and still see drug resistance emerging in some individuals. The next step is to fully understand exactly how this genetic variant controls HIV replication.”
McLaren PJ, Porreca I, Iaconis G et al. Africa-specific human genetic variation near CHD1L associates with HIV-1 load. Nature 2 August 2023; doi: 10.1038/s41586-023-06370-4
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