COWPOX VIRUS GENOME ENCODES A 2ND SOLUBLE HOMOLOG OF CELLULAR TNF RECEPTORS, DISTINCT FROM CRMB, THAT BINDS TNF BUT NOT LT-ALPHA

We show the cowpox genome (Brighten 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 tw o potential N-linked glycosylation sites. The similar to 25-kDa recomb inant protein binds TNF specifically and completely inhibits TN F-medi ated cytolysis. The strongest sequence homologues are the ligand-bindi ng regions of the type II cellular TNF receptor (TNFRII) and CrmB, a d istinct pox virus gene also encoding a soluble TNF binding protein. Un like TNFRII and CrmB, CrmC does not bind lymphotoxin (LT alpha, TNF be ta) and lacks the conserved (but nonhomologous) similar to 150-residue C-terminal domain of CrmB proteins. The presumed function of CrmC is viral inhibition of host-elicited TNF. (C) 1996 Academic Press, Inc.