The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines

Alshad S. Lalani, Kathryn Graham, Karen Mossman, Krishna Rajarathnam, Ian Clark-Lewis, David Kelvin, Grant McFadden

Research output: Contribution to journalArticle

141 Scopus citations

Abstract

The myxoma virus T7 protein M-T7 is a functional soluble gamma interferon receptor homolog that has previously been shown to hind gamma interferon and inhibit its antiviral activities in a species-specific manner, but gene knockout analysis has suggested a further role for M-T7 in blocking leukocyte influx into infected lesions. We purified M-T7 to apparent homogeneity and showed that M-T7 is an N-linked glycoprotein that appears to be a stable homotrimer with a molecular mass of approximately 113 kDa in solution. M-T7, in addition to forming inhibitory complexes with rabbit gamma interferon, was also shown to bind to human interleukin-8, a prototypic member of the chemokine superfamily. Moreover, M-T7 was able to interact promiscuously with all members of the CXC, CC, and C chemokine subfamilies tested. Binding of human RANTES to M-T7 can be competed by rabbit gamma interferon and also by cold RANTES competitor with a 50% inhibitory concentration of 900 nM. Although M-T7 retains binding to a number of interleukin-8 N-terminal (ELR) deletion mutants, binding to mutants containing deletions in the C-terminal heparin-binding domain of interleukin- 8 is abrogated. Furthermore, heparin effectively competes the interaction of M-T7 with the chemokine RANTES but not with rabbit gamma interferon. We propose that this novel M-T7 interaction with members of the chemokine superfamily may be facilitated through the conserved heparin-binding domains found in a wide spectrum of chemokines and that M-T7 may function by modulating chemokine-glycosaminoglycan interactions in virus-infected tissues.

Original languageEnglish (US)
Pages (from-to)4356-4363
Number of pages8
JournalJournal of virology
Volume71
Issue number6
DOIs
StatePublished - Jun 1997

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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