Post-translational modification of the myxoma-virus anti-inflammatory serpin SERP-1 by a virally encoded sialyltransferase

Piers Nash, Michele Barry, Bruce T. Seet, Kirstin Veugelers, Susy Hota, Jody Heger, Carley Hodgkinson, Kathryn Graham, Ronald J. Jackson, Grant McFadden

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

SERP-1 is a secreted serpin (serine-proteinase inhibitor) encoded by myxoma virus, a poxvirus pathogen of rabbits. SERP-1 is required for myxoma-virus virulence, and the purified protein has been shown to possess independent anti-inflammatory activity in animal models of restenosis and antigen-induced arthritis. As an inhibitor of serine proteinases, SERP-1 acts against tissue-type plasminogen activator, urokinase-type plasminogen activator, plasmin, thrombin and Factor Xa. In the present study, examination of SERP-1 glycosylation-site muta nts showed that the N-linked glycosylation of Asn172 was essential for SERP-1 secretion, whereas mutation of Asn99 decreased secretion efficiency, indicating that N-linked glycosylation plays an essential role in the processing and trafficking of SERP-1. Furthermore, comparison of SERP-1 from wild-type myxoma virus and a virus containing a targeted disruption of the MST3N sialyltransferase locus demonstrated that SERP-1 is specifically modified by this myxoma-virus-encoded sialyltransferase, and is thus the first reported viral protein shown to by modified by a virally encoded glycosyltransferase. Sialylation of SERP-1 bq the MST3N gene product creates a uniquely charged species of secreted SERP-1 that is distinct from SERP-1 produced from other eukaryotic expression systems, though this has no apparent effect upon the kinetics of in vitro proteinase inhibition. Rather, the role of viral sialylation of SERP-1 likely relates to masking antigenicity or targeting SERP-1 to specific sites of action in vitro.

Original languageEnglish (US)
Pages (from-to)375-382
Number of pages8
JournalBiochemical Journal
Volume347
Issue number2
DOIs
StatePublished - Apr 15 2000

Keywords

  • Glycosylation
  • Poxvirus
  • Proteinase
  • Sialylation
  • Virulence factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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