T2 open reading frame from the shope fibroma virus encodes a soluble form of the TNF receptor

Craig A. Smith, Terri Davis, Janis M. Wignall, Wenie S. Din, Theresa Farrah, C. Upton, Douglas McFadden, Raymond G. Goodwin

Research output: Contribution to journalArticle

177 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)335-342
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume176
Issue number1
DOIs
StatePublished - Apr 15 1991
Externally publishedYes

Fingerprint

Rabbit Fibroma Virus
Tumor Necrosis Factor Receptors
Viruses
Open Reading Frames
Cytokines
Nerve Growth Factor Receptor
Recombinant proteins
Cytokine Receptors
Immune system
COS Cells
Nerve Growth Factor
Sequence Homology
Recombinant Proteins
Immune System
Glycoproteins
Membrane Proteins

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

T2 open reading frame from the shope fibroma virus encodes a soluble form of the TNF receptor. / Smith, Craig A.; Davis, Terri; Wignall, Janis M.; Din, Wenie S.; Farrah, Theresa; Upton, C.; McFadden, Douglas; Goodwin, Raymond G.

In: Biochemical and Biophysical Research Communications, Vol. 176, No. 1, 15.04.1991, p. 335-342.

Research output: Contribution to journalArticle

Smith, Craig A. ; Davis, Terri ; Wignall, Janis M. ; Din, Wenie S. ; Farrah, Theresa ; Upton, C. ; McFadden, Douglas ; Goodwin, Raymond G. / T2 open reading frame from the shope fibroma virus encodes a soluble form of the TNF receptor. In: Biochemical and Biophysical Research Communications. 1991 ; Vol. 176, No. 1. pp. 335-342.
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