Analysis of the function of cytoplasmic fibers formed by the rubella virus nonstructural replicase proteins

Abstract 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...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2010-10, Vol.406 (2), p.212-227
Main Authors: Matthews, Jason D, Tzeng, Wen-Pin, Frey, Teryl K
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cell-to-cell spread
Cercopithecus aethiops
Cytoplasm - metabolism
Cytoplasm - virology
Humans
Infectious Disease
Microtubule organizing center
Microtubule-Organizing Center - metabolism
Microtubule-Organizing Center - virology
Microtubules
Molecular Sequence Data
Mutation
Protein Structure, Secondary
Protein Structure, Tertiary
Rubella - metabolism
Rubella - virology
Rubella virus
Rubella virus - genetics
Rubella virus - physiology
Rubella virus replicase protein fibers
Vero Cells
Viral Nonstructural Proteins - chemistry
Viral Nonstructural Proteins - genetics
Viral Nonstructural Proteins - metabolism
Virus Replication
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Summary:Abstract 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 α-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 α-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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2010.07.025