Role of SNARE proteins in HIV-1 assembly and release

Texas Tech University Health Scis Center, Lubbock TX

Investigators

Abstract

DESCRIPTION (provided by applicant): Viruses have a limited number of genes but a complex life cycle. They have hence evolved to utilize numerous host factors to complete their replication. With regard to HIV-1 assembly, a synchronized movement of different viral proteins to specific sites on the plasma membrane enables virion morphogenesis. The host SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) proteins are widely involved in late stages of vesicular mediated transport. These proteins catalyze the docking and fusion of apposing membranes in the vesicle and target compartment. The SNAREs are involved not only in the endocytic and exocytic trafficking pathways but also in other membrane fusion and fission events. These include daughter cell separation during cytokinesis, a phenomenon that bears striking similarity to the process of HIV-1 budding. By generalized disruption of the SNARE sorting machinery, we recently demonstrated a role for these proteins in HIV-1 assembly by affecting Gag localization to the plasma membrane. Preliminary data suggests that SNARE proteins may regulate the cellular trafficking pathways required for Gag association/transport with the plasma membrane. In this study, we propose to define the precise mechanism via which SNARE disruption affects HIV particle production. We aim to study the effects of SNARE disruption on the cellular proteins and lipid components important for HIV particle production. We will also determine if SNARE disruption affects the integrity of the cellular membrane architecture. Finally, we propose to study whether there is a preferential involvement of specific v (vesicle-associated) or t (target membrane-associated) SNARE proteins in this process. This will not only define a role for novel host factors in the HIV life ccle but a better understanding of the virus assembly and release pathway will help open avenues for identifying novel anti-viral targets.