Format

Send to

Choose Destination
See comment in PubMed Commons below
J Virol. 2013 Nov;87(22):12003-19. doi: 10.1128/JVI.01960-13. Epub 2013 Sep 4.

The amino-terminal domain of alphavirus capsid protein is dispensable for viral particle assembly but regulates RNA encapsidation through cooperative functions of its subdomains.

Author information

1
Department of Microbiology, University of Alabama, Birmingham, Alabama, USA.

Abstract

Venezuelan equine encephalitis virus (VEEV) is a pathogenic alphavirus, which circulates in the Central, South, and North Americas, including the United States, and represents a significant public health threat. In recent years, strong progress has been made in understanding the structure of VEEV virions, but the mechanism of their formation has yet to be investigated. In this study, we analyzed the functions of different capsid-specific domains and its amino-terminal subdomains in viral particle formation. Our data demonstrate that VEEV particles can be efficiently formed directly at the plasma membrane without cytoplasmic nucleocapsid preassembly. The entire amino-terminal domain of VEEV capsid protein was found to be dispensable for particle formation. VEEV variants encoding only the capsid's protease domain efficiently produce genome-free VEEV virus-like particles (VLPs), which are very similar in structure to the wild-type virions. The amino-terminal domain of the VEEV capsid protein contains at least four structurally and functionally distinct subdomains, which mediate RNA packaging and the specificity of packaging in particular. The most positively charged subdomain is a negative regulator of the nucleocapsid assembly. The three other subdomains are not required for genome-free VLP formation but are important regulators of RNA packaging. Our data suggest that the positively charged surface of the VEEV capsid-specific protease domain and the very amino-terminal subdomain are also involved in interaction with viral RNA and play important roles in RNA encapsidation. Finally, we show that VEEV variants with mutated capsid acquire compensatory mutations in either capsid or nsP2 genes.

PMID:
24006447
PMCID:
PMC3807903
DOI:
10.1128/JVI.01960-13
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center