University of Delaware, 163 The green, 177 Brown Laboratory, Newark, DE, 19716


Wednesday, October 18, 2017 - 16:00 to 17:30
TRIM5α is cellular factor that prevents HIV-1 infection in certain organisms (i.e. old world monkeys) and possibly certain human cell lines.. Although the exact mechanism of how TRIM5alpha blocks infection is still unclear, TRIM5alpha recognizes the incoming mature HIV-1 capsid, which is a cone-shaped fullerene shell composed of ~1,500 copies of the virally encoded CA protein. The CA subunits form a two-dimensional array of CA hexamers that is closed by incorporation of 12 CA pentamers. Recognition of the capsid by TRIM5alpha leads to accelerated capsid dissociation, disrupted reverse transcription, and enhanced interferon signaling.
We have found that TRIM5α assembles into a hexagonal net-like lattice that matches the symmetry and spacing of the capsid lattice. We have also shown that CA hexagonal lattices can induce TRIM5alpha assembly and that TRIM5alpha can wrap around bona fide HIV-1 cores. Most recently, using hybrid approach of EM and X-ray crystallography, we have developed a high resolution mode for the TRIM hexaganol lattice on the CA surface. Our work supports a model wherein TRIM5α constitutes a soluble surveillance mechanism in the cell that intercepts and disables incoming retroviral capsids.