# The evolution of envelope function during coinfection with phylogenetically distinct human immunodeficiency virus

## TL;DR

This study shows that coinfection with different HIV-1 variants can lead to more infectious viruses through recombination, potentially speeding up disease progression.

## Contribution

The study reveals that recombination during HIV-1 coinfection can enhance viral infectivity and fitness through envelope protein changes.

## Key findings

- Emergent recombinants outcompeted co-transmitted HIV variants within 52 weeks, showing higher entry efficiency.
- Recombination in the gp41 region of the envelope protein likely increased fusogenicity and pseudovirus entry efficiency.
- Higher pseudovirus entry efficiency correlated with lower CD4+ T cell counts, suggesting increased virulence.

## Abstract

Coinfection with two phylogenetically distinct Human Immunodeficiency Virus-1 (HIV-1) variants might provide an opportunity for rapid viral expansion and the emergence of fit variants that drive disease progression. However, autologous neutralising immune responses are known to drive Envelope (Env) diversity which can either enhance replicative capacity, have no effect, or reduce viral fitness. This study investigated whether in vivo outgrowth of coinfecting variants was linked to pseudovirus and infectious molecular clones’ infectivity to determine whether diversification resulted in more fit virus with the potential to increase disease progression.

For most participants, emergent recombinants displaced the co-transmitted variants and comprised the major population at 52 weeks postinfection with significantly higher entry efficiency than other co-circulating viruses. Our findings suggest that recombination within gp41 might have enhanced Env fusogenicity which contributed to the increase in pseudovirus entry efficiency. Finally, there was a significant correlation between pseudovirus entry efficiency and CD4 + T cell count, suggesting that the enhanced replicative capacity of recombinant variants could result in more virulent viruses.

Coinfection provides variants with the opportunity to undergo rapid recombination that results in more infectious virus. This highlights the importance of monitoring the replicative fitness of emergent viruses.

The online version contains supplementary material available at 10.1186/s12879-024-09805-z.