On the trail of genetically determined resilience: Researchers have discovered a genetic peculiarity in people of African descent that is associated with a low HIV viral load. As a result, the carriers have a lower risk of transmission and the progression of the disease is slowed down. The insight into the basics of natural resilience could lead to the further development of new treatment approaches, say the scientists.
Despite major advances in treatment, HIV/AIDS is still a huge health problem for mankind: almost 40 million people worldwide are infected and up to 1.5 million more are infected every year. The virus attacks the immune cells of those affected and impairs their ability to fight the pathogen or cause of the disease. This makes them susceptible to infections and cancer - AIDS threatens their lives. Anyone who has access to antiretroviral therapy can be spared the onset of immune deficiency today. However, there is still no cure or vaccination against HIV and resistance to the drugs can develop. Therefore, there is still an urgent need to explore new ways of fighting HIV/AIDS.
One approach is to examine the background of some people's natural resistance to the spread of the virus in the body. Because the mechanism could possibly be used therapeutically. In this context, it is known that some people develop a comparatively low viral load in their blood after an infection. This value is associated with a delayed progression of the disease and a lower risk of further spread of the infection. Apparently, these people have certain genetic predispositions that at least counteract the multiplication of the virus in the body.
Genome-Wide Association Study
Genetic peculiarities that are associated with a certain effect can now be uncovered by so-called genome-wide association studies. It involves analyzing the genomes of large numbers of people to identify genetic variants that are linked to a clinical outcome, such as the ability to naturally control viral replication. An international team of researchers has now specifically applied this method to people of African descent. Up to now, this group has not been the focus of relevant studies, although the chance of success is comparatively high. The genetic diversity of people in Africa is particularly high.
As part of their study, the scientists analyzed the DNA of almost 4,000 HIV-infected people of African descent. They were able to link the genetic data with information on the infection status and the development of the viral load in these people. Using computer analysis and genetic mapping techniques, they then tracked down a peculiarity on chromosome 1 that is associated with a reduced viral load. It is becoming apparent that between four and 13 percent of people of African descent are carriers of this trait.
Medical potential
The variation was found to affect a gene called CHD1L. This inheritance is already known to lead to the production of a protein that plays a role in repairing damaged DNA. However, a connection with HIV has not yet been demonstrated. In order to prove fundamentally that CHD1L actually has something to do with the development of the viral load, the team carried out experimental studies on immune cells that are infected by the HI virus and serve to replicate it. To do this, the researchers used stem cells to generate versions of the white blood cells in which the activity of CHD1L was restricted. In this way, at least fundamentally, they were able to demonstrate an effect of CHD1L in connection with HIV: the virus multiplies better in macrophages when the gene in them is switched off.
Although many questions remain unanswered, the study results now appear very promising, the researchers say: "This gene appears to be important for controlling viral load in some people of African descent," says co-author Harriet Groom from the University of Cambridge. Although we don't yet know exactly how this works, it gave us important clues. The connection between HIV replication in macrophages and viral load is particularly interesting and unexpected,” says the scientist. The team will therefore now conduct further investigations into the question of what role CHD1L plays in HIV infections and why the discovered variant influences virus replication.
As they emphasize, the main goal is a practical contribution to medical development: insights into the genetic basis of natural resistance could lead to improved treatment options for infected people. "Our results provide insights into potential therapeutic targets needed to continue the fight against HIV," says co-author Jacques Fellay from the Ecole Polytechnique Fédérale de Lausanne. "Furthermore, our results underscore the importance of conducting genome studies in different population groups," says the scientist.
Source: University of Cambridge, Ecole Polytechnique Fédérale de Lausanne, professional article: Nature, doi: 10.1038/s41586-023-06370-4