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Replication of the rotavirus genome requires an active ubiquitin-proteasome system

Tomás López1, Daniela Silva-Ayala, Susana López

  • 1Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, UNAM, Avenida Universidad 2001, Colonia Chamilpa, Cuernavaca, Morelos 62210, Mexico. tdlopez@ibt.unam.mx

Journal of Virology
|September 9, 2011
PubMed

Insights

The ubiquitin-proteasome system is crucial for rotavirus replication. Its inhibition impairs viral genome replication and protein incorporation, highlighting a complex interplay with virus life cycle.

Area of Science:

  • Virology
  • Cellular Biology
  • Biochemistry

Background:

  • Rotavirus (RRV) is a significant human pathogen.
  • The role of cellular machinery in rotavirus replication is not fully understood.

Purpose of the Study:

  • To investigate the role of the ubiquitin-proteasome system in rotavirus replication.
  • To elucidate the specific mechanisms by which this system affects viral propagation.

Main Methods:

  • Treatment of MA104 cells with proteasome inhibitor MG132.
  • Analysis of viral protein synthesis, genome replication, and virion assembly.
  • Utilizing cells with temperature-sensitive mutations in ubiquitin-activating enzyme E1.
  • Assessing the effect of ubiquitin overexpression.

Main Results:

  • MG132 treatment inhibited rotavirus replication, viral genome replication, and protein incorporation into viroplasms, despite restoring protein synthesis with nonessential amino acids.
  • A temperature-sensitive mutation in E1 ubiquitin-activating enzyme reduced rotavirus progeny yield.
  • Overexpression of ubiquitin partially rescued virus yield in MG132-treated cells.

Conclusions:

  • The ubiquitin-proteasome system is essential for efficient rotavirus replication.
  • Both ubiquitination and proteolytic activities of the system are important for the rotavirus life cycle.
  • The system influences viral genome replication and protein complex formation.

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