Role of the myxoma virus soluble CC-chemokine inhibitor glycoprotein, M- T1, during myxoma virus pathogenesis

Alshad S. Lalani, Jennefer Masters, Kathryn Graham, Liying Liu, Alexandra Lucas, Grant McFadden

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

Myxoma virus is a poxvirus that causes a virulent systemic disease called myxomatosis in European rabbits. Like many poxviruses, myxoma virus encodes a variety of secreted proteins that subvert the antiviral activities of host cytokines. It was recently demonstrated that the myxoma virus M-T1 glycoprotein is a member of a large poxvirus family of secreted proteins that bind CC-chemokines and inhibit their chemoattractant activities in vitro. To determine the biological role of M-T1 in contributing to myxoma virus virulence, we constructed a recombinant M-T1-deletion mutant virus that was defective in M-T1 expression. Here, we demonstrate that M-T1 is expressed continuously during the course of myxoma virus infection as a highly stable 43-kDa glycoprotein and is dispensable for virus replication in vitro. Deletion of M-T1 had no significant effects on disease progression or in the overall mortality rate of infected European rabbits but heightened the localized cellular inflammation in primary tissue sites during the initial 2 to 3 days of infection. In the absence of M-T1 expression, deep dermal tissues surrounding the primary site of virus inoculation showed a dramatic increase in infiltrating leukocytes, particularly monocytes/macrophages, but these phagocytes remained relatively ineffective at clearing virus infection, likely due to the concerted properties of other secreted myxoma virus proteins. We conclude that M-T1 inhibits the chemotactic signals required for the influx of monocytes/macrophages during the acute-phase response of myxoma virus infection in vivo, as predicted by its ability to bind and inhibit CC- chemokines in vitro.

Original languageEnglish (US)
Pages (from-to)233-245
Number of pages13
JournalVirology
Volume256
Issue number2
DOIs
StatePublished - Apr 10 1999
Externally publishedYes

ASJC Scopus subject areas

  • Virology

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