Structure of a Venezuelan equine encephalitis virus assembly intermediate isolated from infected cells.
Venezuelan equine encephalitis virus (VEEV) is a prototypical enveloped ssRNA virus of the family Togaviridae. To better understand alphavirus assembly, we analyzed newly formed nucleocapsid particles (termed pre-viral nucleocapsids) isolated from infected cells. These particles were intermediates along the virus assembly pathway, and ultimately bind membrane-associated viral glycoproteins to bud as mature infectious virus. Purified pre-viral nucleocapsids were spherical with a unimodal diameter distribution. The structure of one class of pre-viral nucleocapsids was determined with single particle reconstruction of cryo-electron microscopy images. These studies showed that pre-viral nucleocapsids assembled into an icosahedral structure with a capsid stoichiometry similar to the mature nucleocapsid. However, the individual capsomers were organized significantly differently within the pre-viral and mature nucleocapsids. The pre-viral nucleocapsid structure implies that nucleocapsids are highly plastic and undergo glycoprotein and/or lipid-driven rearrangements during virus self-assembly. This mechanism of self-assembly may be general for other enveloped viruses.
Lamb
Kristen
K
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-0647, USA.
Lokesh
G L
GL
Sherman
Michael
M
Watowich
Stanley
S
D000524:Alphavirus / Q000737:chemistry / Q000302:isolation & purification / Q000502:physiology / Q000648:ultrastructure; D000818:Animals; D006224:Cricetinae; D004666:Encephalitis Virus, Venezuelan Equine / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology* / Q000648:ultrastructure; D004685:Encephalomyelitis, Venezuelan Equine / Q000821:virology*; D006801:Humans; D008958:Models, Molecular; D019251:Nucleocapsid / Q000737:chemistry / Q000302:isolation & purification / Q000648:ultrastructure; D019065:Virus Assembly