The genetic architecture of HIV-1 virulence
 In a study published in Virus Evolution, Blanquart et al. investigated how viral genetic variation contributes to differences in HIV-1 virulence. Using whole-genome HIV sequences from more than 2,200 seroconverters across Europe, the authors conducted the largest genome-wide association study (GWAS) of HIV virulence to date. The study was based on data from the international BEEHIVE collaboration, with the Swiss HIV Cohort Study (SHCS) contributing the largest national cohort.
The researchers analysed viral genetic variants in relation to set-point viral load (SPVL), a key marker of HIV disease progression and transmissibility, as well as CD4 cell decline. They found that viral genetic factors explain around 25–26% of the variation in SPVL, confirming that HIV virulence is partly determined by the viral genome itself. In contrast, viral genetics had little influence on the rate of CD4 cell decline.
The study identified two immune escape mutations with significant effects on viral load. One mutation in the gag gene was associated with lower viral load, while a mutation in the nef gene was linked to higher viral load. Both mutations are known to help HIV evade host immune responses mediated by specific HLA molecules.
The findings further suggest that HIV virulence has a highly polygenic architecture, meaning that many viral variants with individually small effects together influence disease severity. The authors conclude that HIV-1 virulence has substantial evolutionary potential and that interactions between viral and host genetics are central to understanding HIV pathogenesis and disease progression.