March 2, 2024

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Higher HIV viral load can impact the virus’s evolution

Higher HIV viral load can impact the virus’s evolution



Higher HIV viral load can impact the virus’s evolution

A recent paper in the journal “Molecular Biology and Evolution” reveals that individuals with a higher viral load of HIV in their bodies also exhibit a higher rate of viral recombination.

Essentially, as the quantity of HIV viruses in the blood increases, the likelihood of viral mutations also rises.

One of the reasons HIV has been historically challenging to combat is its exceptionally high recombination rate. Recombination allows different strains of the virus to exchange genetic information, propelling HIV’s evolution within the human body. This exchange of genetic information helps the virus evade the immune system’s pursuit and develop resistance to drugs designed to treat HIV.

In a broader context, recombination is a crucial driving force for evolution, enabling organisms to eliminate detrimental mutations and combine beneficial ones. Despite its importance, scientists still lack a complete understanding of how the recombination rate of HIV changes during the infection process or between different individuals. Understanding the factors influencing recombination rates in well-studied systems like HIV can help reveal the broader implications of recombination on evolution.

An understudied aspect of HIV recombination is co-infection, where two different virus particles infect the same cell. While interest in HIV recombination has been longstanding, it remains unclear whether variations in co-infection rates lead to changes in recombination rates. Although studies on HIV in cell cultures and mice suggest a link between increased co-infection and an increase in recombinant viruses, it’s uncertain if this effect exists in individuals infected with HIV.

The researchers involved in this study hypothesized that individuals with a higher viral load (more HIV in the blood) would have more cells simultaneously infected, leading to a higher recombination rate. To test this hypothesis, they developed a new method called “Recombination Analysis through Time Series Linkage Decay” (RATS-LD), which quantifies recombination by leveraging genetic associations between mutations that change over time.

The investigation revealed that, while the recombination rates of the lowest one-third of the HIV population with the lowest viral load aligned with previous estimates, the median recombination rate of the highest one-third of the viral load group was nearly six times higher. Additionally, the researchers observed that within individual bodies, both viral load and effective recombination rate increased simultaneously.

These findings suggest that the recombination rate of the HIV virus may be more extreme than previously believed. Apart from the HIV virus, many organisms, such as bacteria and plants, do not necessarily require recombination for reproduction but can benefit from it. The researchers’ discovery also indicates that population density may influence the efficiency of recombination in various scenarios.

“In recent decades, the explosive growth of sequencing data has deepened geneticists’ understanding of recombination rates, showing that recombination rates can depend on context and be influenced by many different molecular factors,” said Elena V. Romero, one of the authors of the paper. “Here, we demonstrate that population density may be one of the previously underestimated viral factors.”

Higher HIV viral load can impact the virus's evolution

Higher HIV viral load can impact the virus’s evolution

References:

Elena Romero et al, Elevated HIV viral load is associated with higher recombination rate in vivo, Molecular Biology and Evolution (2023). DOI: 10.1093/molbev/msad260.

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