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Vaccinia virus E3 protein prevents the antiviral action of ISG15

Susana Guerra1, Ana Cáceres, Klaus-Peter Knobeloch

  • 1Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología CSIC, Campus Universidad Autónoma, Madrid, Spain. sguerra@cnb.csic.es

Plos Pathogens
|July 8, 2008
PubMed

Insights

The ubiquitin-like modifier ISG15 acts as a host defense against vaccinia virus (VACV). ISG15 deficiency enhances VACV replication and pathogenesis, with the virus E3 protein suppressing ISG15

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Type I interferons (IFN) induce ISG15, a ubiquitin-like modifier.
  • ISG15's role in host defense against viral infections is under investigation.

Purpose of the Study:

  • To investigate the role of ISG15 in host defense against vaccinia virus (VACV).
  • To elucidate the mechanism of ISG15's antiviral activity against VACV.

Main Methods:

  • Utilized ISG15-deficient murine embryo fibroblasts (MEFs) and mice.
  • Employed vaccinia virus strains, including a deletion mutant (VVDeltaE3L).
  • Used siRNA and lentivirus vectors to modulate ISG15 expression; performed immunoprecipitation analysis.

Main Results:

  • ISG15 deficiency enhanced VACV replication and VVDeltaE3L growth in MEFs.
  • ISG15-deficient mice exhibited increased disease and mortality upon VVDeltaE3L infection.
  • VACV E3 protein binds ISG15 and suppresses its antiviral activity, independent of PKR.
  • Enhanced lung inflammation observed in ISG15-deficient mice infected with VACV mutants.

Conclusions:

  • ISG15 functions as a crucial host defense molecule against VACV infection.
  • The viral E3 protein antagonizes ISG15's antiviral activity.
  • ISG15 plays a significant role in controlling VACV pathogenesis and associated inflammation.

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