To know what are the natural factors of the human being that allow it check for HIV has allowed the scientific community to design most of the 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 may favor the control of HIV.
The discovery, published in the magazine Nature, was born from the genomic study of 3,879 people living with HIV and having African ancestors. In particular, the change is close to CHD1L gene located on chromosome 1 and appears to mainly affect macrophages, cells with a key role in the immune system and in maintaining the persistence of HIV. Until now, this genetic modification had not been detected in previous studies involving mainly Caucasians. Understanding the role of this gene in HIV infection could give it 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 characteristics of the host, such as its genetics.
We wanted to focus on people of African descent to also learn about the genetics of this population, which is heavily affected by the HIV pandemic.
“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 found 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 previously studied the genomes of 6,000 people living in Europe and North America. Therefore, they detected a variant in chromosome 6 linked to HIV control.
“Now, we wanted to focus on people of African descent to also learn about the genetics of this population, which is heavily affected by the HIV pandemic,” he explains. Giuseppe Maria MiroSenior 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
As part of the International Consortium for HIV Genomics, the research team analyzed the genomes of 3,879 people of African descent infected with HIV and the amount of virus they have in their blood in the absence of antiretroviral treatment. In this way it was possible to identify which ones genetic variants they are present in people who have fewer viruses in their blood and therefore control HIV replication better.
“We confirmed the presence of the genetic variant on chromosome 6 that was previously found in a population of European ancestry, but we also detected a new one on chromosome 1,” comments Martínez-Picado. Specifically, this genetic change is very close to the CHD1L gene and could affect its expression.
We confirmed the presence of the genetic variant on chromosome 6 that was previously found in a population of European descent, but we also detected a new one on chromosome 1
To understand what role this gene plays in HIV infection, the team carried out various experiments in the laboratory with cells genetically modified to express or not express CHD1L. They were thus 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 activating the immune response and maintaining the viral reservoir. “Although we have yet to determine the precise mechanism by which this genetic change is able to limit HIV replication, the results suggest that this gene is involved in the 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 conducting genomic studies in populations of different origins to better address the specific medical needs of each person and avoid global health inequalities,” notes Martínez-Picado.
Large-scale genetic studies that analyze genomes of large human populations, such as the one recently published, would allow to broaden the knowledge on 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.