Higher viral load during HIV infection may shape viral evolution

A new paper in Molecular biology and evolution finds that HIV-positive populations in people with higher viral loads also have higher rates of viral recombination. Indeed, the more HIV there is in the blood, the easier it is for the virus to diversify.

One of the reasons HIV has always been so difficult to combat is the virus’s exceptionally high recombination rate. Recombination allows the exchange of genetic information between strains of the virus and drives the evolution of HIV within people. This genetic exchange helps the virus evade the immune system and become resistant to many drugs designed to treat HIV.

More generally, recombination is an important evolutionary driver, allowing organisms to purge destructive mutations and combine beneficial mutations. Despite its importance, scientists do not yet understand how the rate of HIV recombination varies over the course of an infection or between different people. Understanding the factors that influence the rate of recombination in a well-studied system such as HIV can help uncover some of the effects of recombination on evolution more broadly.

An important, but understudied, step in HIV recombination is coinfection, in which two different viral particles infect the same cell. Despite long-standing interest in HIV recombination, we do not yet understand whether variation in the rate of coinfection could lead to variation in the rate of recombination. Although studies of HIV in cell cultures and mice have demonstrated that increased co-infection is associated with increased recombinant viruses, it is unclear whether this effect is found in people living with HIV. HIV.

Researchers involved in the new study hypothesized that people with higher viral loads (more HIV in the blood) would have more co-infected cells, leading to higher rates of virus recombination. To study this hypothesis, they developed a new approach called Recombination Analysis via Time Series Linkage Decay (RATS-LD) to quantify recombination using genetic associations between mutations over time.

This investigation found that while HIV populations with viral loads in the bottom third of the dataset have recombination rates consistent with previous estimates, populations with viral loads in the top third have a median recombination rate near six times higher. Additionally, researchers observe patterns of viral load and effective recombination rates increasing simultaneously in individual individuals.

These results suggest that HIV recombination rates may be even more extreme than researchers previously recognized. Beyond HIV, many organisms like bacteria and plants do not need to recombine to reproduce, but can benefit from it. To exchange genetic material, these organisms also rely on the meeting of two different genomes in the same place and at the same time. For this reason, the researchers’ results also suggest that population density could influence the effective rate of recombination in several contexts.

“An explosion of sequencing data over the past several decades has allowed geneticists to better understand that recombination rates can be context-dependent and are influenced by many different molecular factors,” said Elena V. Romero, one of the authors of the article. “Here we show that population density may be one of these previously underestimated factors for viruses.”