Development of a latency model for HIV-1 subtype C and the impact of long terminal repeat element genetic variation on latency reversal

This study set out to create a laboratory model to study latency—a state where HIV remains hidden and inactive—in the context of HIV‑1 subtype C, which is the most common form of the virus in sub‑Saharan Africa but has been under‑studied compared with subtype B found in Europe and North America. Latent virus reservoirs are a major barrier to curing HIV because standard treatment doesn’t eliminate these hidden viruses. To address this, the researchers engineered a simplified viral system that carries both a marker (green fluorescent protein) and a key HIV regulatory protein controlled by the subtype C viral promoter region (LTR). They used this to infect laboratory T cells and human immune cells to mimic latent infection.

Using this model, they showed that the subtype C promoter region is less easily reactivated from latency than the subtype B version when cells are treated with various agents meant to “wake up” latent virus. They also found that natural genetic differences within subtype C LTR sequences from people living with HIV led to different levels of reactivation, suggesting that the exact genetic makeup of this region influences how readily latency can be reversed. In particular, variants with more copies of a specific binding site were associated with lower reactivation potential. These findings indicate that both differences between subtypes and variation within subtype C affect how the virus hides and reactivates.

The model provides a tool for future research on therapies aimed at reversing latency and highlights the need to consider viral genetic variation when designing cure strategies.

Disclaimer: This lay summary was generated by AI and has not been approved by any of the authors yet.