2023-08-02 11:00:01
To know what are the natural factors of the human being that allow control HIV it has allowed the scientific community to design the majority of treatment and cure strategies developed to date. Now, an international study, with the participation of the IrsiCaixa AIDS Research Institute and the Hospital Clínic Barcelona-IDIBAPS, identifies a new genetic variant that would favor HIV control.
The discovery, published in the journal Nature, arises from the genomic study of 3,879 people living with HIV and who have African ancestors. Specifically, the change is close to the have CHD1L located on chromosome 1 and seems to mainly affect macrophages, cells with a key role in the immune system and maintenance of HIV persistence. Until now, in previous studies carried out mainly with Caucasian people, this genetic modification had not been detected. Understanding the role of this gene in HIV infection could give it a potential use as a therapeutic target.
The progress of HIV infection is different for each person, and can depend on a wide variety of factors related to the virus, the environment, or the characteristics of the host, such as its genetics.
We wanted to focus on people of African descent to also know the genetics of this population, highly affected by the HIV pandemic.
Josep Maria Miró, professor of medicine
“There are people who, despite living with an active HIV infection, the amount of virus they have in their blood is below the standard threshold detected in the rest of the people who suffer from the infection,” he explains. Javier Martinez-Picado, ICREA researcher at IrsiCaixa and one of the authors of the article. To understand the role of host genetics in this phenomenon, the team had previously studied the genome of 6,000 people living in Europe and North America. Thus, they detected a variant in chromosome 6 linked to the control of HIV.
“Now, we wanted to focus on people of African descent to also know the genetics of this population, highly affected by the HIV pandemic,” he details. Joseph Maria MiróSenior Consultant of the Infectious Diseases Service of the Clínic Barcelona, group leader of IDIBAPS and CIBERINFEC and professor of Medicine at the University of Barcelona.
Less HIV infection in macrophages, cells with a key role in viral persistence
Within the framework of the International Consortium for HIV Genomics, the research team has analyzed the genome of 3,879 people of African descent with HIV infection, and the amount of virus they have in their blood in the absence of antiretroviral treatment. In this way, it has been possible to identify which genetic variants they are present in people who have less virus in their blood and therefore better control HIV replication.
“We have confirmed the presence of the genetic variant of chromosome 6 that had been previously found in a population of European descent, but we have also detected a new one on chromosome 1”, comments Martínez-Picado. Specifically, this genetic change is very close to the CHD1L gene, and could be affecting its expression.
We have confirmed the presence of the genetic variant of chromosome 6 that had previously been found in a population of European descent, but we have also detected a new one on chromosome 1
Javier Martínez-Picado, ICREA researcher
To understand what role this gene plays in HIV infection, the team has carried out various experiments in the laboratory with genetically modified cells to express or not express CHD1L. Thus, they have been able to demonstrate that, in cells that do not express the gene, HIV replicates with greater difficulty. Specifically, the most affected cells are the macrophages, involved in the activation of the immune response and the maintenance of the viral reservoir. “Although we have yet to determine the precise mechanism by which this genetic change manages to limit HIV replication, the results suggest that this gene is involved in early stages of the virus cycle, and that its effect is specifically concentrated in certain cells of the body. ”, says Miro.
The path towards inclusive and impactful research
Despite the high incidence of HIV infection in the African population, it is underrepresented in human genomics studies. “The results show the importance of carrying out genomic studies in populations of different ancestry to better address the specific medical needs of each person and avoid global health inequalities,” Martínez-Picado remarks.
Large-scale genetic studies that analyze genomes of large human populations, such as the one recently published, would allow expanding knowledge about the impact of host genetics on the response to infections. “Characterizing in detail all the genetic variables that allow better control of HIV infection allows us to have new therapeutic targets and have different flanks from which to attack the virus,” concludes Miró.
Fuente: SINC
Rights: Creative Commons.
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