title: Dynamics of herpes simplex virus capsid maturation visualized by time-lapse cryo-electron microscopy.
abstract: The capsid of the herpes simplex virus initially assembles as a procapsid that matures through a massive conformational change of its 182 MDa surface shell. This transition, which stabilizes the fragile procapsid, is facilitated by the viral protease that releases the interaction between the shell and the underlying scaffold; however, protease-deficient procapsids mature slowly in vitro. To study procapsid maturation as a time-resolved process, we monitored this reaction by cryo-electron microscopy (cryo-EM). The resulting images were sorted into 17 distinct classes, and three-dimensional density maps were calculated for each. When arranged in a chronological series, these maps yielded molecular movies of procapsid maturation. A single major switching event 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, the major capsid protein.
authors.affiliation: Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: J Bernard
authors.initials: JB
authors.lastname: Heymann
authors.forename: Naiqian
authors.initials: N
authors.lastname: Cheng
authors.forename: William W
authors.initials: WW
authors.lastname: Newcomb
authors.forename: Benes L
authors.initials: BL
authors.lastname: Trus
authors.forename: Jay C
authors.initials: JC
authors.lastname: Brown
authors.forename: Alasdair C
authors.initials: AC
authors.lastname: Steven
mesh_terms: D000818:Animals; D002213:Capsid / Q000648:ultrastructure*; D002460:Cell Line; D006224:Cricetinae; D020285:Cryoelectron Microscopy / Q000379:methods; D018259:Herpesvirus 1, Human / Q000254:growth & development / Q000648:ultrastructure*; D007091:Image Processing, Computer-Assisted; D018139:Simplexvirus / Q000254:growth & development / Q000648:ultrastructure*