Phenotypic Characterization of Subtype A and Recombinant AC Transmitted/Founder Viruses from a Rwandan HIV-1 Heterosexual Transmission Cohort

This study generated and tested primary HIV‑1 isolates that were responsible for establishing infection in people from a Rwandan heterosexual transmission group. The focus was on subtype A and recombinant AC virus subtypes, which are common in parts of East Africa but less represented in research studies. Using blood samples taken soon after infection, the researchers built 20 infectious molecular clones representing the actual viruses that initially spread in each person’s body. They then measured how these viruses behave in the lab.

The team found that the capacity at which these viruses replicate in immune cells varied widely by more than fifty‑fold among primary derived individual infectious clones, suggesting that even closely related viruses can behave quite differently. Many of the differences in replication were linked to mutation in a viral protein amino acid sequence called Gag.

These viruses all used the same entry route into cells (via the CCR5 co-receptor). When tested against a panel of broadly neutralizing antibodies a type of immune defence that vaccines aim to trigger most viruses were sensitive to an antibody targeting the CD4 binding site on the virus, especially N6. Other antibodies showed good potency against some but not all viruses, and one antibody (10E8V4) acted broadly but only at higher doses.

This well‑characterized panel of subtype A and AC recombinant viruses provides an important resource for future research on how different virus types affect transmission, disease progression, and HIV vaccine development.