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 Citations (Scopus)

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
StatePublished - Jun 1997
Externally publishedYes

Fingerprint

Myxoma virus
heparin
chemokines
interferon-gamma
Chemokines
Heparin
Chemokine CCL5
Interferon-gamma
receptors
Interleukin-8
interleukin-8
Rabbits
rabbits
C Chemokines
CXC Chemokines
CC Chemokines
Gene Knockout Techniques
mutants
Glycosaminoglycans
glycosaminoglycans

ASJC Scopus subject areas

  • Immunology

Cite this

Lalani, A. S., Graham, K., Mossman, K., Rajarathnam, K., Clark-Lewis, I., Kelvin, D., & McFadden, G. (1997). The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines. Journal of Virology, 71(6), 4356-4363.

The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines. / Lalani, Alshad S.; Graham, Kathryn; Mossman, Karen; Rajarathnam, Krishna; Clark-Lewis, Ian; Kelvin, David; McFadden, Grant.

In: Journal of Virology, Vol. 71, No. 6, 06.1997, p. 4356-4363.

Research output: Contribution to journalArticle

Lalani, AS, Graham, K, Mossman, K, Rajarathnam, K, Clark-Lewis, I, Kelvin, D & McFadden, G 1997, 'The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines', Journal of Virology, vol. 71, no. 6, pp. 4356-4363.
Lalani, Alshad S. ; Graham, Kathryn ; Mossman, Karen ; Rajarathnam, Krishna ; Clark-Lewis, Ian ; Kelvin, David ; McFadden, Grant. / The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines. In: Journal of Virology. 1997 ; Vol. 71, No. 6. pp. 4356-4363.
@article{d4f464bdb20144609625751876622063,
title = "The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines",
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.",
author = "Lalani, {Alshad S.} and Kathryn Graham and Karen Mossman and Krishna Rajarathnam and Ian Clark-Lewis and David Kelvin and Grant McFadden",
year = "1997",
month = "6",
language = "English (US)",
volume = "71",
pages = "4356--4363",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "6",

}

TY - JOUR

T1 - The purified myxoma virus gamma interferon receptor homolog M-T7 interacts with the heparin-binding domains of chemokines

AU - Lalani, Alshad S.

AU - Graham, Kathryn

AU - Mossman, Karen

AU - Rajarathnam, Krishna

AU - Clark-Lewis, Ian

AU - Kelvin, David

AU - McFadden, Grant

PY - 1997/6

Y1 - 1997/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0031010760&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031010760&partnerID=8YFLogxK

M3 - Article

VL - 71

SP - 4356

EP - 4363

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 6

ER -