Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein.
Supernatants from vaccinia virus (VV)-infected CV-1 cells were examined and found to contain a 33 kd protein capable of binding murine interleukin-1 beta (mIL-1 beta). A VV open reading frame (ORF) that exhibits 30% amino acid identity to the type II IL-1 receptor was expressed in CV-1-EBNA cells and shown specifically to bind mIL-1 beta. A similar ORF from cowpox virus was expressed and also specifically bound mIL-1 beta. A recombinant VV was constructed in which this ORF was disrupted (vB15RKO). Supernatants from vB15RKO-infected cells did not contain an IL-1-binding protein. Supernatants from VV-infected CV-1 cells were capable of inhibiting IL-1-induced murine lymphocyte proliferation in vitro while supernatants from vB15RKO infected cells did not. Intracranial inoculation of mice with vB15RKO suggests that this ORF is involved in VV virulence. The possible role of a virus-encoded IL-1-binding protein in the pathology of a poxvirus infection and its relationship to other poxvirus-encoded immune modulators is discussed.
Spriggs
M K
MK
Department of Molecular Biology, Immunex Research and Development Corporation Seattle, Washington 98101.
Hruby
D E
DE
Maliszewski
C R
CR
Pickup
D J
DJ
Sims
J E
JE
Buller
R M
RM
VanSlyke
J
J
D000818:Animals; D002460:Cell Line; D015608:Cowpox virus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D003470:Culture Media / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D003470:Culture Media; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D014764:Viral Proteins; C067847:B15R protein, Vaccinia virus