TY - JOUR
T1 - T2 open reading frame from the shope fibroma virus encodes a soluble form of the TNF receptor
AU - Smith, Craig A.
AU - Davis, Terri
AU - Wignall, Janis M.
AU - Din, Wenie S.
AU - Farrah, Theresa
AU - Upton, C.
AU - McFadden, G.
AU - Goodwin, Raymond G.
N1 - Funding Information:
We thank Christy McNutt and Rita Jerzy for expert.technical for valuable discussions. G.M. is supported by the Alberta Research and the National Cancer Institute of Canada.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1991/4/15
Y1 - 1991/4/15
N2 - A transcriptionally active open reading frame (T2) from Shope Fibroma Virus was recently shown to have striking sequence homology with members of a new superfamily of cell surface proteins, including a receptor for human tumor necrosis factor (1). Here we report that recombinant T2 protein expressed in COS cells is a soluble, secreted glycoprotein which specifically binds human TNFα and β, and inhibits binding of these cytokines to native TNF receptors on cells. T2 binding of TNF is not inhibited by nerve growth factor, although the nerve growth factor receptor is also a member of the same family, nor by nine other recombinant cytokines. Further, the repeating domain structure of T2 most closely resembles that of the type I TNF receptor (p75) and is significantly different from other family members, including the type II TNF receptor (p55). Since T2 possesses a leader sequence but lacks a transmembrane domain, these results confirm the original suggestion (1) that T2 represents a soluble form of the type I TNF receptor which is secreted from virally infected cells, and whose function is to immunosupress the host by abrogating the potentially destructive effects of TNF. This is the first such virally-encoded soluble cytokine receptor to be identified, and may represent a more general mechanism by which viruses subvert the host immune system.
AB - A transcriptionally active open reading frame (T2) from Shope Fibroma Virus was recently shown to have striking sequence homology with members of a new superfamily of cell surface proteins, including a receptor for human tumor necrosis factor (1). Here we report that recombinant T2 protein expressed in COS cells is a soluble, secreted glycoprotein which specifically binds human TNFα and β, and inhibits binding of these cytokines to native TNF receptors on cells. T2 binding of TNF is not inhibited by nerve growth factor, although the nerve growth factor receptor is also a member of the same family, nor by nine other recombinant cytokines. Further, the repeating domain structure of T2 most closely resembles that of the type I TNF receptor (p75) and is significantly different from other family members, including the type II TNF receptor (p55). Since T2 possesses a leader sequence but lacks a transmembrane domain, these results confirm the original suggestion (1) that T2 represents a soluble form of the type I TNF receptor which is secreted from virally infected cells, and whose function is to immunosupress the host by abrogating the potentially destructive effects of TNF. This is the first such virally-encoded soluble cytokine receptor to be identified, and may represent a more general mechanism by which viruses subvert the host immune system.
UR - http://www.scopus.com/inward/record.url?scp=0025816054&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025816054&partnerID=8YFLogxK
U2 - 10.1016/0006-291X(91)90929-2
DO - 10.1016/0006-291X(91)90929-2
M3 - Article
C2 - 1850261
AN - SCOPUS:0025816054
SN - 0006-291X
VL - 176
SP - 335
EP - 342
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -