Two vaccinia virus proteins structurally related to the interleukin-1 receptor and the immunoglobulin superfamily.
The structures of two vaccinia virus genes (B15R and B18R) from near the right inverted terminal repeat are described. These genes encode proteins of 36.5K and 40.7K, respectively, which have an N-terminal hydrophobic sequence, possible sites for attachment of N-linked carbohydrate and a short string of hydrophobic residues near the C terminus. These properties are consistent with the mature proteins being either virion, cell surface or secretory glycoproteins. Protein sequence comparisons established that the two gene products are related to each other (20% identity) and to the immunoglobulin (Ig) superfamily. Intriguingly, the nearest homologues of these proteins in the SWISS-PROT (version 14) database are the human and murine interleukin-1 receptors, although both proteins are related to a wide range of Ig superfamily members, including the interleukin-6 receptor. The product of one of these genes is known to be expressed on the cell surface early during infection and immunity directed against it confer resistance to virus infection without directly neutralizing virus infectivity. We propose a novel method for virus immune evasion in which the product of one or both of these proteins may bind interleukin-1 and/or interleukin-6 and prevent these cytokines reaching their natural receptors. In consequence the inflammatory response would be diminished and virus replication enhanced.
Smith
G L
GL
Sir William Dunn School of Pathology, University of Oxford, U.K.
Chan
Y S
YS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004279:DNA, Viral / Q000737:chemistry*; D016208:Databases, Factual; D015252:Deoxyribonucleases, Type II Site-Specific; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics; D007375:Interleukin-1; D051379:Mice; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals / Q000737:chemistry / Q000235:genetics; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics; D017472:Receptors, Interleukin-1; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014616:Vaccinia virus / Q000235:genetics*; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*
D004279:DNA, Viral; D007136:Immunoglobulins; D007375:Interleukin-1; D021382:Protein Sorting Signals; D011971:Receptors, Immunologic; D017472:Receptors, Interleukin-1; D014764:Viral Proteins; C067853:B18R protein, Vaccinia virus; C067847:B15R protein, Vaccinia virus; D015252:Deoxyribonucleases, Type II Site-Specific; C029792:GTCGAC-specific type II deoxyribonucleases