UC San Diego

HIV has killed millions of people since its discovery in the 1980s and continues to be a costly disease that affects millions worldwide. The advent of antiretroviral drug-therapy made this once deadly disease manageable through a daily regimen of drugs. However, there is still no cure or preventative vaccine, largely due to the virus’s genetic diversity and ability to evolve to escape the host immune system. More information about HIV’s infection mechanisms and accessory proteins is needed to advance further towards a cure. This research study focused on two HIV proteins, Env and Nef, and their relationship with a human host cell protein, SERINC5. Env is essential for viral infectivity and is responsible for fusing virus particles into target cells, but its activity seems to be counteracted by SERINC5. Nef antagonizes the SERINC-effect. Envs and Nefs from 10 transmitted/founder (T/F) patient clones were analyzed with and without SERINC5 using infectivity and ELISA assays to determine how infectivity varies with these different proteins. The Env expression constructs were not evaluable, but the Nef expression constructs showed expected decreased infectivity in the presence of overexpressed SERINC5, as well as varying effectiveness in enhancing infectivity and counteracting SERINC5. Sequence alignments of the 10 T/F Nefs with the consensus sequence Nef revealed variations in several Nef sequence motifs that might explain Nef’s varying effectiveness. This study indicates that Nefs from different infected patients have varying abilities to counteract SERINC5, increasing our understanding about this HIV accessory protein’s role in viral infectivity, and its potential roles in viral transmission and replication.