Envelope Glycoprotein Incorporation and Function

Division Of Basic Sciences - Nci

Investigators

Linked publications, trials & patents

Abstract

This project is focused on the mechanism of Env glycoprotein incorporation into virus particles and the putative interactions between the gp41 CT and the MA domain of Gag. We have also been investigating host cell proteins that antagonize the function of viral envelope glycoproteins including HIV-1 Env. Our work in this area has focused on two families of interferon-inducible proteins: the membrane-associated RING CH domain (MARCH) family of E3 ubiquitin ligases and the guanylate binding proteins (GBPs). We and others have found that the antiviral activity of MARCH8 and GBP5 extends to distantly related viral envelope glycoproteins such as MLV Env, VSV-G, EboV GP, and SARS-CoV-2 S protein. Our current focus is on GBP5 and the related protein GBP2. If time, personnel, and resources allow, we will also pursue further mechanistic studies on MARCH8. This research seeks to elucidate the antiviral properties of these poorly understood components of the host innate immune response. We are pursuing cryoEM as a tool to understand the influence of the long gp41 cytoplasmic tail on gp120 structure and the observation (made independently by us and Chris Aiken's lab) that particle maturation influences the fusogenic activity of the Env complex in a gp41 cytoplasmic tail-dependent manner. Specific research aims in this project are a) Define the structural elements in Gag and Env that regulate HIV Env incorporation and function, and b) Characterize the function of host factors that restrict viral envelope glycoprotein incorporation.