Journal
VIROLOGY
Volume 406, Issue 2, Pages 212-227Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2010.07.025
Keywords
Rubella virus; Rubella virus replicase protein fibers; Microtubules; Microtubule organizing center; Cell-to-cell spread
Categories
Funding
- NIH [AI21389]
- Molecular Basis of Disease Area of Focus Fellowship
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The P150 and P90 replicase proteins of rubella virus (RUBV), a plus-strand RNA Togavirus, produce a unique cytoplasmic fiber network resembling microtubules. Pharmacological and mutagenic approaches were used to determine if these fibers functioned in virus replication. The pharmacological approach revealed that microtubules were required for fiber formation, but neither was necessary for virus replication. Through the mutagenic approach it was found that alpha-helices near both termini of P150 were necessary for fiber assembly and infectivity, but fiber formation and viability could not be correlated because most of these mutations were lethal. The N-terminal alpha-helix of P150 affected both proteolytic processing of P150 and P90 from the P200 precursor and targeting of P200, possibly through directing conformational folding of P200. Finally, we made the unexpected discovery that RUBV genomes can spread from cell-to-cell without virus particles, a process that we hypothesize utilizes RUBV-induced cytoplasmic projections containing fibers and replication complexes. (C) 2010 Elsevier Inc. All rights reserved.
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