The Torbett Lab studies HIV-1 entry, evolution, and viral assembly at the genomic, biochemical and structural levels, as well as human hematopoietic stem and progenitor cell resistance of lentiviral vector entry and delivery. We study HIV evolution to viral inhibitor and immune pressures and have developed long-read sequencing and computational methods to follow individual viruses within a population to provide insights as to where and how compensatory mutations arise to support viral fitness. 

HIV Gag and Gag-Pol are capable of self-assembly in vitro, although it is generally accepted that during cellular infection, cellular factors play a decisive role for immature Gag and Gag-Pol trafficking and virion assembly resulting in HIV production. However, less is known about the composition, dynamics, and function of cellular proteins that may contribute to Gag and Gag-Pol virion assembly and cellular trafficking to the ESCRT pathway resulting in viral budding. To interrogate the Gag-host cell protein interactome, we have focused on identifying proteins that interact with Gag and Gag-Pol during cellular trafficking and assembly through innovative protein proximal labeling and mass spectrometry and then determining the function of identified protein via CRISPR methodologies. 

For lentiviral vectors or virus-like particles to be effective in a clinical setting for delivering new genes or to modify genes, the delivery procedure must be efficient and safe. Our group has helped to pioneer lentiviral vector gene delivery strategies for blood stem and immune B cells in a research setting. We have found conditions that minimizes in vitro cell treatment time and maximizes the number of cells targeted by lentiviral vectors. These procedural improvements may be of importance for advancing the fields of gene therapy for the clinical purposes. Our current studies are focused on the identification of small molecules and changes in lentiviral vectors that improve and make more safe in vitro gene delivery to blood stem and B cells. Lastly, unraveling the mechanisms whereby hematopoietic stem cells, myeloid, and lymphocytes restrict lentiviral viral entry and regulate cellular responses will allow this “cellular restriction code” to be translated and then applied to viral vectors and nanoparticles to transport gene payloads to desired cell populations in the body for direct, in vivo, gene correction of human diseases.