For the first time in over two decades, researchers have identified a genetic variant associated with HIV infection. The work, published in the journal Nature, could further our understanding of the disease and contribute to future therapies.
A global disease
Human immunodeficiency virus (HIV) is a retrovirus that progressively weakens an individual’s immune system, by infecting cells such as CD4+ T cells, macrophages and dendritic cells. Almost 40 million people are living with HIV globally, but the majority of these individuals live in Africa. Despite this, research has focused disproportionately on those of European ancestry.
HIV has been consistently researched over the last few decades, but many aspects of the infection process remain unknown. A number of genetic variants that contribute to an individual’s HIV susceptibility have been identified, but this does not paint the full picture. In the current study, researchers have identified a new variant that appears to be associated with a reduced viral load.
The viral load
In a GWAS of over 4,000 individuals of African ancestry, the team found a significant locus in chromosome 1. The variant in question lay between a long-non-coding RNA and the DNA repair gene CHD1L. Further analysis revealed that the variant only appeared in African-ancestry genomes, with the frequency depending on geographical region. This result was mirrored in different cohorts.
The variant is associated with reduced viral load; in the simplest terms, the amount of the virus that is present in a patient’s body. A lower viral load is generally correlated with better disease response and decreased transmission rates. Therefore, an understanding of this mechanism could contribute to better to disease control and treatment.
To elucidate the role of CHD1L in HIV replication, the researchers knocked-out expression of the gene in various immune cells. They discovered that reduced CDH1L expression leads to increased HIV replication in macrophages. This result suggested that CDH1L is necessary to control the levels of HIV replication, and subsequent viral load.
The importance of diversity
Speaking in a press release, author Harriet Groom stated: “This gene seems to be important to controlling viral load in people of African ancestry. 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. The link between HIV replication in macrophages and viral load is particularly interesting and unexpected.”
Whilst much remains unknown about HIV infection, these results shed light on a mechanism specific to African individuals, highlighting the importance of diversity in genomics research. The findings could also contribute to future therapies. By reducing viral load on a large-scale, transmission rates could decrease significantly.