HIV-1 subtype C Nef-mediated SERINC5 down-regulation significantly contributes to overall Nef activity

Nef is an HIV protein which plays a crucial role in the virus’s ability to evade the immune system and replicate efficiently, through performing multiple activities in infected cells. Nef counteracts a host protein called SERINC5, which is known to inhibit the spread of HIV, by reducing the levels of SERINC5 in cells infected by the virus. This Nef activity significantly enhances viral infectivity.  Understanding the interaction between Nef and SERINC5 is crucial for developing new strategies to combat HIV, particularly HIV subtype C which is the most common strain of the virus.

In this study, the Nef proteins from 106 different individuals with HIV subtype C infection were studied for their ability to reduce SERINC5 in infected cells.  Mutations that affect the ability of the subtype C Nef protein to down-regulate SERINC5 were identified.  In previous work, other Nef activities had been measured for the same patient-derived Nef proteins.  An analysis of the relative contribution of each Nef activity to overall Nef function showed that SERINC5 down-regulation was likely the strongest contributor of the Nef activities measured. 

Overall, this research sheds light on the relative importance of different Nef activities and identifies potential genetic determinants of this Nef activity that may have relevance for design of vaccines or therapeutics.

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.