Cowpox virus genome encodes a second soluble homologue of cellular TNF receptors, distinct from CrmB, that binds TNF but not LT alpha.
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.
Smith
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Immunex Corporation, Seattle, Washington 98101, USA. Smithc@immunex.com
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Smith
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Richards
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Smolak
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Goodwin
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Pickup
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D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D015608:Cowpox virus / Q000235:genetics* / Q000502:physiology; D004279:DNA, Viral; D005814:Genes, Viral; D016679:Genome, Viral; D006801:Humans; D008233:Lymphotoxin-alpha / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000378:metabolism; D014779:Virus Replication
D004279:DNA, Viral; D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D014764:Viral Proteins; C089458:crmB protein, Orthopoxvirus