Analysis of the transport modes of nuclear herpesvirus capsids

• Applicant: Professor Dr. Jens Bernhard Bosse
• Subject Area: Virology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 240572849

Herpesviruses are important and widespread pathogens of animals and humans. Currently nine human herpesviruses are known. They are associated with a wide variety of human disease while vaccines are only available for one of them, stressing the need for small drug leads that can inhibit essential viral processes.Herpesviruses replicate in the nucleus of the host cell. Viral capsids then assemble in the nuclear space, are packaged with the viral genome and then leave the nucleus by budding through the nuclear membranes. While the last years showed huge progress in the understanding of these individual processes, not much is known about how capsids transverse the nuclear space on their way out. Biophysical studies have shown that inert particles of similar size cannot diffuse over longer distances in the nucleus.The goal of this project is to reveal how nuclear herpesvirus capsids move through the nucleus. To that end we will use high-speed 3D imaging of living, infected cells. Tracks of individual capsids in the three-dimensional space will be used to calculate their respective transport modes. Depending on the mode found (active, energy-dependent or passive diffusion) we will proceed with specific experiments targeted to find the mechanism by which the observed transport mode leads to efficient capsid flux.This analysis will be repeated with members of all three herpesvirus subfamilies in an effort to define the basic machinery needed for nuclear capsid transport. Ultimately, this might lead to the definition of new drugs targeting the conserved core machinery of herpesviruses.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Lynn W. Enquist, Ph.D.