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Biological Physics Seminar (CPLC): Alex Evilevitch, “Herpesvirus infectivity facilitated by internal DNA pressure”

Event Type
Yann Chemla
144 Loomis
Sep 8, 2017   2:00 pm  
Alex Evilevitch, University of Illinois at Urbana-Champaign
Sandra Patterson
Originating Calendar
Physics - Physics of Living Cells Seminar

Herpesviruses are a leading cause of human viral disease, second only to influenza and cold viruses. Herpesviruses consist of a double-stranded (ds) DNA genome contained within a protein shell, termed the capsid, that is surrounded by an unstructured protein layer (the tegument) and a lipid-envelope. During viral replication, an ATP-dependent motor packages the genome into a preformed capsid through a unique opening created by the portal complex. Herpes Simplex virus type 1 (HSV-1) is a prototypical model system to study the general infection mechanisms of herpesviruses and other viruses that release their genome into the cell nucleus without capsid disassembly. We have recently shown that HSV-1 genome packaging creates an internal pressure of tens of atmospheres within the viral capsid. This pressure results from bending stress and repulsive forces acting on the tightly packaged DNA molecule. Between rounds of replication, the virion must be sufficiently stable to ensure that the packaged genome is retained within the capsid. Conversely, during infection the virion must be unstable enough to allow genome release into the cell nucleus. A precise balance between these physical aspects of the viral capsid and its encapsidated genome is crucial to the viral replication cycle. Using HSV-1 as our primary model system, we investigate the roles of intracapsid DNA pressure, mobility and capsid stability for viral replication with respect to retention of the packaged genome inside the capsid and its subsequent ejection during infection. These studies provide new insights into the key mechanisms facilitating as well as inhibiting Herpes infectivity.

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