Cowpox virus genome encodes a second soluble homologue of cellular TNF receptors, distinct from CrmB, that binds TNF but not LT alpha

Virology. 1996 Sep 1;223(1):132-47. doi: 10.1006/viro.1996.0462.

Abstract

We show the cowpox genome (Brighton Red strain) contains a single copy gene, crmC, expressed at late times during viral infection, encoding a soluble, secreted protein whose sequence marks it as a new member of the TNF receptor family. The cysteine-rich protein contains 186 amino acids, the N-terminal 21 of which constitute a signal peptide, and two potential N-linked glycosylation sites. The approximately 25-kDa recombinant protein binds TNF specifically and completely inhibits TNF-mediated cytolysis. The strongest sequence homologues are the ligand-binding regions of the type II cellular TNF receptor (TNFRII) and CrmB, a distinct pox virus gene also encoding a soluble TNF binding protein. Unlike TNFRII and CrmB, CrmC does not bind lymphotoxin (LT alpha, TNF beta) and lacks the conserved (but nonhomologous) approximately 150-residue C-terminal domain of CrmB proteins. The presumed function of CrmC is viral inhibition of host-elicited TNF.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Chick Embryo
  • Cowpox virus / genetics*
  • Cowpox virus / physiology
  • DNA, Viral
  • Genes, Viral
  • Genome, Viral
  • Humans
  • Lymphotoxin-alpha / metabolism
  • Mice
  • Molecular Sequence Data
  • Receptors, Tumor Necrosis Factor / antagonists & inhibitors
  • Receptors, Tumor Necrosis Factor / genetics*
  • Receptors, Tumor Necrosis Factor / metabolism
  • Sequence Homology, Amino Acid
  • Solubility
  • Transcription, Genetic
  • Tumor Cells, Cultured
  • Viral Proteins / metabolism
  • Virus Replication

Substances

  • DNA, Viral
  • Lymphotoxin-alpha
  • Receptors, Tumor Necrosis Factor
  • Viral Proteins
  • crmB protein, Orthopoxvirus

Associated data

  • GENBANK/U55052