Serp1, a serine proteinase inhibitor encoded by myxoma virus, is a secreted glycoprotein that interferes with inflammation

Joanne L. Macen, Chris Upton, Nick Nation, Douglas McFadden

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Myxoma virus is a leporipoxvirus that causes a rapidly lethal, generalized infection known as myxomatosis in the European rabbit (Oryctolagus cuniculus). A characteristic feature of myxomatosis is the specific downregulation of key pathways important for numerous host defenses against the viral infection. The SERP1 gene has significant sequence similarity to the serpin superfamily of serine proteinase inhibitors and is one of many virulence factor genes located within the terminal regions of the myxoma virus genome. Transcriptional analysis of the SERP1 gene in myxoma virus (strain Lausanne) indicates that it is expressed as a late gene and studies using a polyclonal anti-SERP1 antiserum indicate that it encodes a secreted protein with an apparent molecular weight of 55 kDa. Using myxoma virus and recombinant vaccinia virus constructs for experiments with tunicamycin and peptide N-glycosidase F, it is shown that the secreted SERP1 protein is modified by N-linked glycosylation. Mutation of both copies of the SERP1 gene in myxoma virus results in a significant attenuation of the virus, such that more than 50% of infected animals are able to recover from the otherwise lethal infection. Histological analyses of lesions taken from infected animals suggest that in the absence of the SERP1 protein, a more effective inflammatory response occurs, allowing a more rapid resolution of the infection. This suggests that SERP1 contributes to viral pathogenesis by interacting with cellular component(s) involved in the regulation of inflammation.

Original languageEnglish (US)
Pages (from-to)348-363
Number of pages16
JournalVirology
Volume195
Issue number2
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

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Myxoma virus
Serine Proteinase Inhibitors
Glycoproteins
Inflammation
Genes
Leporipoxvirus
Infection
Mannosyl-Glycoprotein Endo-beta-N-Acetylglucosaminidase
Rabbits
Serpins
Tunicamycin
Proteins
Vaccinia virus
Virulence Factors
Virus Diseases
Glycosylation
Immune Sera
Down-Regulation
Molecular Weight
Genome

ASJC Scopus subject areas

  • Virology

Cite this

Serp1, a serine proteinase inhibitor encoded by myxoma virus, is a secreted glycoprotein that interferes with inflammation. / Macen, Joanne L.; Upton, Chris; Nation, Nick; McFadden, Douglas.

In: Virology, Vol. 195, No. 2, 01.01.1993, p. 348-363.

Research output: Contribution to journalArticle

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