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

Jason D Matthews1, Wen-Pin Tzeng, Teryl K Frey

  • 1Georgia State University, Department of Biology, Atlanta, GA 30303, USA.

Virology
|August 11, 2010
PubMed

Insights

Rubella virus (RUBV) replicase proteins form fiber networks, but these are not essential for virus replication. Unexpectedly, RUBV can spread between cells via cytoplasmic projections without forming infectious virus particles.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • Rubella virus (RUBV), a Togavirus, encodes P150 and P90 replicase proteins.
  • These proteins assemble into a unique cytoplasmic fiber network that structurally resembles cellular microtubules.

Purpose of the Study:

  • To investigate the role of RUBV-induced cytoplasmic fibers in viral replication.
  • To elucidate the function of P150 protein domains in viral processes.

Main Methods:

  • Pharmacological disruption of microtubules.
  • Mutagenesis of P150 protein domains.
  • Analysis of viral replication, infectivity, and protein processing.

Main Results:

  • Microtubules are necessary for fiber formation but not for RUBV replication.
  • Specific α-helices in P150 are crucial for fiber assembly and infectivity.
  • Mutations affecting these α-helices often proved lethal, decoupling fiber formation from viability.
  • The N-terminal α-helix of P150 influences proteolytic processing and cellular targeting of viral precursors.
  • RUBV can spread cell-to-cell via cytoplasmic projections, independent of infectious virus particles.

Conclusions:

  • RUBV-induced cytoplasmic fibers are not essential for viral replication.
  • P150 protein structure, particularly N-terminal α-helices, is critical for processing, targeting, and infectivity.
  • RUBV exhibits cell-to-cell spread through novel mechanisms involving cytoplasmic projections and replication complexes.

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