Nolan Rivera
Research Mentor(s): Akira Ono
Mentor Department: Microbiology & Immunology
Authors: Nolan Rivera, Rajat Mudgal, Akira Ono
Session: Session 1 (9:00am – 9:50am)
Presentation Type: Poster 27
Abstract
HIV is one of leading causes of death among infectious diseases, affecting about 40 million people worldwide. While there are viral suppression treatments available, at present there is no way to completely eradicate the virus, which leads to proliferation of virus from latent reservoirs. HIV virion formation is facilitated via a poorly understood mechanism by the HIV-1 Gag polyprotein, specifically guiding virus particle assembly to phosphatidylinositol 4,5-bisphosphate (PIP2)-positive membranes, which is primarily the plasma membranes. We hypothesize that the specificity of the Gag polyprotein to membranes containing PIP2 may be caused by an interaction between the MA domain of the Gag protein and tRNA-SeC(TCA), which was found to have a high binding affinity to HIV Gag in a recent RNA sequence study. Using alphafold, we predicted the SeCTCA tRNA to interact with the MA domain on three of its four arms, being the D-arm, variable arm, and TpsiC-arm. Knowing this, we have purified MA protein via recombinant protein expression and affinity chromatography and transcribed in-vitro the tRNA-SeC carrying arm deletions. We are currently using a liposome binding assay to quantify Gag protein’s binding affinity to different acidic phospholipids, including PIP2, in the presence or absence of either the wild type or mutants of tRNA-SeC. This data allows us to determine which interactions between Gag’s MA domain and the tRNA-SeC cause an inhibition in Gag’s binding to PIP2-positive and PIP2-negative membranes. This information may pave the way for new therapies that can target this interaction to reduce HIV Gag’s binding to the plasma membrane.
