Tatiana Domitrovic, Ph.D.

Research

The mechanism by which non-enveloped viruses breach host membranes remains poorly understood. Recent findings indicate that small hydrophobic or amphipathic peptides produced by the cleavage of the capsid subunit are responsible for the destabilization of the bilayer integrity, and consequently, virus internalization. Understanding this process in molecular detail is important not only for the design of new antiviral agents, but also for developing therapeutic strategies based on virus capsids as delivery vehicles for RNAi into the cell. We are focusing on a highly accessible model system, the Nudaurelia Capensis Omega Virus (N?W), to investigate the mechanism of membrane disruption by nonenveloped virus. This icosahedral virus undergoes a maturation process driven by an autocatalytic cleavage of the capsid protein generating the lytic peptide ?. Specific mutations can induce an arrest in this process given rise to partially matured particles, whose structures have been recently characterized with high resolution. Therefore, N?W is a unique tool to understand how the maturation process relates to ? exposure and the lytic properties of the virus particle. The results of this research will directly impact the development of a refined RNAi carriage system based on N?V capsid, and will contribute significantly to the understating of the mechanism of host cell entry by non-enveloped viruses.