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Calicivirus 3C-like proteinase inhibits cellular translation by cleavage of poly(A)-binding protein

Muge Kuyumcu-Martinez1, Gaël Belliot, Stanislav V Sosnovtsev

  • 1Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030, USA.

Journal of Virology
|July 16, 2004
PubMed

Insights

Caliciviruses inhibit cellular translation by cleaving poly(A)-binding protein (PABP). This viral protease strategy disrupts protein synthesis, a mechanism potentially shared across virus families.

Area of Science:

  • Virology
  • Molecular Biology
  • Biochemistry

Background:

  • Caliciviruses, including noroviruses and vesiviruses, are significant human and animal pathogens.
  • Regulation of cellular translation during calicivirus infection remains poorly understood.
  • Poly(A)-binding protein (PABP) is crucial for mRNA stability and translation initiation.

Purpose of the Study:

  • To investigate the role of calicivirus proteases in regulating cellular translation.
  • To determine if caliciviruses cleave poly(A)-binding protein (PABP) during infection.

Main Methods:

  • Utilized recombinant 3C-like proteinases (r3CLpro) from norovirus and feline calicivirus (FCV).
  • Assessed PABP cleavage activity in vitro and in infected cell lines (HeLa, feline kidney).
  • Analyzed the impact of PABP cleavage on mRNA translation efficiency.

Main Results:

  • Norovirus and FCV r3CLpro directly cleaved PABP, generating distinct products.
  • PABP cleavage by norovirus r3CLpro inhibited cellular translation in a poly(A)-dependent manner.
  • PABP cleavage and reduced cellular protein synthesis were observed in FCV-infected cells.

Conclusions:

  • Calicivirus 3CLpro enzymes cleave PABP, similar to poliovirus 3Cpro, as a strategy to inhibit host translation.
  • PABP cleavage disrupts the interaction between PABP's functional domains, impairing translation.
  • PABP cleavage may represent a conserved viral mechanism for manipulating cellular translation across virus families.

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