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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
08:32

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Published on: March 2, 2014

Ovarian tumor domain-containing viral proteases evade ubiquitin- and ISG15-dependent innate immune responses

Natalia Frias-Staheli1, Nadia V Giannakopoulos, Marjolein Kikkert

  • 1Department of Microbiology, Mount Sinai School of Medicine, New York, NY 10029, USA.

Cell Host & Microbe
|December 15, 2007
PubMed

Insights

Viral proteases with ovarian tumor (OTU) domains can remove ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15) from proteins, disrupting innate antiviral defenses and promoting viral infection.

Area of Science:

  • Molecular Biology
  • Virology
  • Immunology

Background:

  • Ubiquitin (Ub) and interferon-stimulated gene product 15 (ISG15) are crucial for innate antiviral responses through protein conjugation.
  • Ovarian tumor (OTU) domain proteins are a superfamily of proteases, with some known to possess Ub-deconjugating activity.

Purpose of the Study:

  • To investigate the deconjugating activity of viral OTU domain-containing proteases.
  • To determine the role of these viral proteases in antagonizing host antiviral mechanisms.

Main Methods:

  • Biochemical assays to assess Ub and ISG15 hydrolysis by viral OTU proteases.
  • In vivo studies using viral protein expression to evaluate effects on antiviral responses and viral susceptibility.
  • Analysis of NF-kappaB signaling pathways.

Main Results:

  • Viral OTU domain-containing proteases from nairoviruses and arteriviruses exhibit broad hydrolytic activity against both Ub and ISG15.
  • This activity contrasts with the specific targets of mammalian OTU domain proteins.
  • Expression of viral OTU proteases antagonizes ISG15's antiviral effects, increases susceptibility to Sindbis virus infection, and inhibits NF-kappaB signaling.

Conclusions:

  • Viral OTU proteases possess a unique deconjugating activity against Ub and ISG15.
  • This viral strategy effectively inhibits host Ub- and ISG15-dependent antiviral pathways, promoting viral pathogenesis.

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