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- Posted August 2, 2023
Gene Could Lower HIV Levels in Some People of African Descent
A newly discovered genetic variant might explain why some people of African ancestry have naturally lower viral loads of HIV, an international team of researchers reports.
This variant, carried by an estimated 4% to 13% of people of African origin, reduces their risk of transmitting the virus and slows the progress of their own illness.
It's the first new genetic variant related to HIV infection discovered in nearly 30 years of research, according to the report, published Aug. 2 in the journal Nature.
This discovery could boost development of new treatments for people living with HIV, said co-lead researcher Harriet Groom, an infectious disease research fellow with the University of Cambridge's department of medicine, in the United Kingdom.
"This gene seems to be important to controlling viral load in people of African ancestry,"Groom said in a university news release. "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."
HIV remains a major threat to global health, with an estimated 38.4 million people living with HIV around the world in 2021, the researchers said in background notes.
Although combination therapies that dramatically reduce HIV viral loads have had a major impact on transmission, 1.5 million people still became newly infected in 2021. That same year, 650,000 people died from AIDS-related illnesses, the study authors added.
Viral load is the amount of a virus in a patient's system. It can vary widely among infected individuals, influenced by a number of factors that include genetics.
Most prior studies of human genetics and HIV have been performed using Europeans. Given that HIV has hit Africa hardest -- more than 25 million people who are HIV-positive live on the continent -- Groom and her colleagues decided to investigate the role of genetics in HIV infection in African populations.
The research team analyzed the DNA of almost 4,000 people of African ancestry living with HIV-1, the most common type of the virus.
Their research discovered a variant within a region on chromosome 1 containing the gene CHD1L, which was associated with reduced viral load in those who carry the mutation.
"African populations are still drastically underrepresented in human DNA studies, despite experiencing the highest burden of HIV infection,"said co-first author Paul McLaren, of the Public Health Agency of Canada's National Microbiology Laboratory. "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."
CHD1L is known to play a role in repairing damaged DNA, but it's not yet clear why the variant might help reduce HIV viral load.
To try to figure that out, researchers generated immune cells in which CHD1L had either been switched off or blunted. HIV tends to attack immune cells.
The investigators found that HIV replicated more efficiently in a type of immune cell called a macrophage when its CHD1L gene was switched off.
But in another immune cell type, the T-cell, there was no effect, even though most HIV replication occurs in T-cells.
"The link between HIV replication in macrophages and viral load is particularly interesting and unexpected,"Groom 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,"said study co-author Manjinder Sandhu, from the Faculty of Medicine at Imperial College London.
More information
The U.S. Centers for Disease Control and Prevention has more about HIV viral load.
SOURCE: University of Cambridge, news release, Aug. 2, 2023
