Barria & Alvarez et al.
Aug 31, 2021
This study investigates the role of an endocytic motif on HIV-1 Env (envelope protein) in modulating the co-transfer of Env and Gag (structural protein) during HIV-1 cell-cell transmission through virological synapses (VSs).
This study investigates the role of an endocytic motif on HIV-1 Env (envelope protein) in modulating the co-transfer of Env and Gag (structural protein) during HIV-1 transmission through virological synapses (VSs) between infected and uninfected T cells. The researchers introduced a biotin acceptor peptide (BAP) tag into the V4 loop of the Env protein to track its trafficking and co-localization with Gag during cell-to-cell transmission.
Key findings:
Biotinylated Env Tracking: The biotin-tagged HIV-1 Env (BAP-V4) did not impair the virus's ability to infect target cells or spread, enabling precise tracking of Env during cell-to-cell transfer.
Endocytic Mutants: Mutations in the endocytic motifs of Env (Y712A and LL855AA) were tested. These mutants showed increased surface accumulation of Env but reduced Gag transfer into target cells. Despite higher Env transfer, these mutants resulted in less productive infection in target cells, indicating that proper Env recycling through endocytosis is essential for effective HIV-1 replication during cell-to-cell transmission.
Co-localization of Gag and Env: The study demonstrated that Gag and Env co-localize at the virological synapse, with specific patterns of Env movement between intracellular pools and the synapse. The altered endocytic trafficking in the Y712A mutant led to higher Env transfer but decreased productive infection, emphasizing the importance of Env's recycling for optimal viral replication.
The findings underscore the importance of Env's endocytosis and recycling in promoting efficient cell-to-cell transfer of HIV-1, influencing both viral transmission and the outcome of infection.