Research

Dynamics of Herpes Simplex Virus Capsid
Maturation Visualized by Time-Lapsed Cryo-EM

J. Bernard Heymann, Naiqian Cheng, William W. Newcomb,

Benes L.Trus, Jay C. Brown and Alasdair C. Steven


The capsid of the herpes simplex virus initially assembles as a precursor procapsid that matures via a massive conformational change of its 192 MDa surface shell. This shell is composed of hexamers and pentamers of VP5 coordinated by heterotrimers of VP19c and VP23. The structural transition, which stabilizes the fragile procapsid, is facilitated by the viral protease which releases the interaction between the shell and the underlying scaffold: however, protease-deficient procapsids mature spontaneously albeit slowly in vitro. We have studied procapsid maturation as a time-resolved process by monitoring this reaction by cryo-electron microscopy. The resulting images were sorted into 17 distinct classes and three-dimensional density maps were calculated for each. Ordered into a time series, these data yielded “molecular movies” of procapsid maturation. A single major convulsion takes place at stages 8-9, preceded by relatively subtle adjustments in the pattern of interactions and followed by similarly small “aftershocks”. The primary mechanism underlying maturation is relative rotations of domains of VP5.


Click on an image to start the movie

Photo of whole capsid from outside view
Whole capsid from outside
 Photo of whole capsid from inside view
Whole capsid from inside
Photo of P-hexon in the center from outside
P-hexon in the center
Photo of P-hexon in the center from inside
P-hexon in the center
Photo of Cut through 2-fold and 5-fold axes
Cut through the 5-fold and 2-fold axes

Prepared by Bernard Heymann, 2002-12-16

 

Updated September 17, 2007