Genetic variant contributes to slower progression of HIV infection

The study identifies a new genetic variant that will slow the progression of HIV infection based on genome analysis of 3,879 people of African descent living with the virus.

The international study was published in the journal Nature with the participation of the AIDS Research Institute IrsiCaixa and the Hospital Clínic Barcelona-Idibaps (northeast Spain).

The discovery was the result of a genomic study of 3,879 people of African descent living with HIV.

In particular, the change is close to the CHD1L gene located on chromosome 1 and appears to mainly affect macrophages, cells that play a key role in the immune system and maintaining HIV persistence, the researchers said in a statement.

Until now, this genetic modification has not been detected in previous studies, conducted mainly with Caucasians, so understanding the role of this gene in HIV infection may allow it to be used as a therapeutic target.

The progression of HIV infection is different for each individual and may depend on a variety of factors related to the virus, environment, or host characteristics such as its genetics.

Spanish researcher Javier Martinez-Picardo explained that “there are people who, despite the fact that they live with active HIV infection, the amount of virus in their blood is below the standard threshold found in other people suffering from this infection.”

To understand the role of host genetics in this phenomenon, the team previously examined the genomes of 6,000 people living in Europe and North America and found a variant on chromosome 6 associated with HIV control.

“Now we wanted to focus on people of African descent in order to also figure out the genetics of this population, which has been hit hard by the HIV pandemic,” explained Josep María Miro, professor of medicine at the Spanish University of Barcelona.

As part of the International HIV Genomics Consortium, a research team analyzed the genomes of 3,879 people of African descent with HIV infection and the amount of virus in their blood when not on antiretroviral treatment.

In this way, they were able to determine which genetic variants are present in people who have less virus in their blood and therefore better control of HIV replication.

“We confirmed the presence of a genetic variant on chromosome 6 that was previously found in a population of European descent, but we also found a new variant on chromosome 1,” Martinez-Picado commented.

In particular, this genetic change is very close to the CHD1L gene and may affect its expression.

To understand the role this gene plays in HIV infection, the team performed several laboratory experiments with cells genetically modified to express or not express CHD1L.

Thus, they were able to demonstrate that in cells that do not express the gene, HIV replicates more difficultly and, in particular, the cells that suffer the most are macrophages involved in activating the immune response and maintaining the virus reservoir.

“While we have yet to determine the exact mechanism by which this genetic change may limit HIV replication, the results indicate that this gene interferes early in the viral cycle and that its action is concentrated in specific cells in the body. ” Miro explained.

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