Genetic variant linked to lower levels of HIV virus in people of African descent
by Jack Stewart
03 August 2023
Image: Graphic representation of DNA.
Credit: Imperial College London
Genetic study identifies Africa-specific variant near CHD1L gene associated with lower HIV-1 viral load in populations of African descent.
New research has found a genetic variant that may explain why some people of African ancestry have naturally lower viral loads of HIV, reducing their risk of transmitting the virus and slowing progress of their own illness.
The paper, published today in Nature, demonstrates the first new genetic variant related to HIV infection discovered in nearly 30 years of research. It could, in the future, help direct the development of new treatments and approaches for those living with HIV.
HIV-1 remains a significant global health crisis, and identifying new targets for therapies is crucial. The study focuses on individuals of African descent due to the disproportionate burden of HIV-1 in Africa and the high genetic diversity in the region.
An international team of researchers analysed the DNA of almost 4,000 people of African ancestry living with HIV-1, the most common type of the virus. They identified a variant within a region on chromosome 1 containing the gene CHD1L which is associated with reduced viral load in carriers of the variant. Between 4% and 13 % of people of African origin are thought to carry this particular variant.
Viral load is the amount of a virus in a patient’s system. Higher levels are known to correlate with faster disease progression and increased risk of transmission. But viral load varies widely among infected individuals, influenced by a number of factors including an individual’s genetic makeup.
Co-Senior author Professor Manjinder Sandhu, Chair in Population Health and Data Science in the School of Public Health, 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 – 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.”
Understanding African populations
Most of what we know about the relationship between our DNA and HIV comes from studies among European populations. But given that HIV disproportionately affects people on the African continent – more than 25 million people who are HIV-positive live on the continent – it’s important to better understand the role of genetics in HIV infection in African populations.
Paul McLaren from the Public Health Agency of Canada’s National Microbiology Laboratory and joint first author on the paper, said: “African populations are still drastically underrepresented in human DNA studies, despite experiencing the highest burden of HIV infection. 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.”
Reducing viral load
CHD1L is known to play a role in repairing damaged DNA, though it is not clear why the variant should be important in reducing viral load. However, as HIV attacks immune cells, researchers at the University of Cambridge’s Department of Medicine, led by Dr Harriet Groom and Professor Andrew Lever, used stem cells to generate variants of cells that HIV can infect in which CHD1L had either been switched off or its activity turned down.
HIV turned out to replicate better in a type of immune cell known as a macrophage when CHD1L was switched off. In another cell type, the T cell, there was no effect – perhaps surprising since most HIV replication occurs in the latter cell type.
Dr Harriet Groom 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, every time we discover something new about HIV control, we learn something new about the virus and something new about the cell. The link between HIV replication in macrophages and viral load is particularly interesting and unexpected.
McLaren, P.J., Porreca, I., Iaconis, G. et al. Africa-specific human genetic variation near CHD1L associates with HIV-1 load. Nature (2023). https://doi.org/10.1038/s41586-023-06370-4
Contact
Dunning, Hayley
Imperial College London
h.dunning@imperial.ac.uk | 020 7594 3278 (on redirect)
Source: https://www.imperial.ac.uk/news/246635/genetic-variant-linked-lower-levels-hiv/
"Reproduced with permission - Imperial College London"
Imperial College London
For more HIV and AIDS News visit...
Positively Positive - Living with HIV/AIDS:
HIV/AIDS News
|
