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A Protocol for Analyzing Hepatitis C Virus Replication
13:04

A Protocol for Analyzing Hepatitis C Virus Replication

Published on: June 26, 2014

Poly(A) binding protein, C-terminally truncated by the hepatitis A virus proteinase 3C, inhibits viral translation

Bo Zhang1, Graziella Morace, Verena Gauss-Müller

  • 1Institute of Medical Molecular Biology, University of Lübeck, Germany.

Nucleic Acids Research
|August 30, 2007
PubMed

Insights

Hepatitis A virus (HAV) proteinase 3C cleaves poly(A)-binding protein (PABP), unlike other viruses. This cleavage regulates viral translation and RNA synthesis by affecting PABP

Area of Science:

  • Molecular Biology
  • Virology
  • Biochemistry

Background:

  • Proteolytic cleavage of translation factors regulates mRNA translation during viral infections and apoptosis.
  • Eukaryotic initiation factor 4G (eIF4G) and poly(A)-binding protein (PABP) are key targets for viral strategies to control host and viral translation.

Purpose of the Study:

  • To investigate the substrate specificity of Hepatitis A virus (HAV) 3C proteinase (3Cpro) regarding translation initiation factors.
  • To elucidate the role of PABP cleavage by HAV 3Cpro in viral translation and replication.

Main Methods:

  • In vitro and in vivo cleavage assays using HAV 3Cpro.
  • Analysis of PABP cleavage products and their functional impact on translation.
  • RNA binding assays to assess the interaction of PABP domains with viral RNA structures.

Main Results:

  • HAV 3Cpro does not cleave eIF4G, differing from coxsackievirus.
  • PABP is cleaved by HAV 3Cpro, separating its N-terminal RNA-binding domain (NTD) from the C-terminal domain.
  • The NTD of PABP inhibits HAV internal ribosome entry site (IRES)-dependent translation and binds to the essential viral RNA element pY1.

Conclusions:

  • PABP cleavage by HAV 3Cpro is a distinct viral mechanism for regulating translation.
  • PABP cleavage and its NTD interaction with viral RNA play a regulatory role in switching between viral translation and RNA synthesis.

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