Ryan T. Behrens
Position title: Sherer Laboratory 2012-Current
Research Title: Exploiting Species-Specific Blocks to Disrupt HIV-1 Gene Expression
Research Description: HIV-1 production is limited in cells derived from mice and other rodents reflecting species-specific incompatibilities between viral regulatory proteins and host cell machinery. One such incompatibility was recently attributed to a structural feature of the murine version of CRM1 (mCRM1), a nuclear export receptor required for viral gene expression. In human cells, the HIV-1 Rev protein recruits CRM1 (hCRM1) to incompletely spliced viral mRNAs and mediates their nuclear export, feeding into virion synthesis pathways. In murine cells, these processes are diminished due to inefficient viral mRNA transport, but the provision of hCRM1 rescues these defects. While the precise mechanism remains unclear, the reduced activity of mCRM1 maps to a discrete, species-specific cluster of amino acids on the outer surface of the protein. Ryan Behren’s research goals are to determine how this structural feature of CRM1 regulates HIV-1 Rev activity and to explore this region as a potential target for antiretroviral therapeutics. Mechanistic insight into how this feature regulates virus output in these cellular contexts will be valuable for informing novel antiviral strategies, understanding retroviral tropism, and developing a small animal rodent model for studying HIV-1 pathogenesis. Ryan’s work has shown that human cells engineered to produce mCRM1 are refractory to HIV-1 virion production if endogenous hCRM1 is inactivated using pharmacological inhibition. His findings support the hypothesis, and current efforts are aimed at using the CRISPR/Cas9 system to engineer a human cell line wherein hCRM1 is replaced with mCRM1.
Ryan has been awarded travel awards from the ASV and the Molecular & Cellular Pharmacology graduate program. He will attend the upcoming CHSL International Meeting and the annual ASV workshop. Ryan plans on defending his dissertation in fall 2018 and continuing his training as a postdoctoral trainee.