Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme.
Cowpox virus effectively inhibits inflammatory responses against viral infection in the chick embryo. This study demonstrates that one of the viral genes necessary for this inhibition, the crmA gene (a cytokine response modifier gene), encodes a serpin that is a specific inhibitor of the interleukin-1 beta converting enzyme. This serpin can prevent the proteolytic activation of interleukin-1 beta, thereby suppressing an interleukin-1 beta response to infection. However, the modification of this single cytokine response is not sufficient to inhibit inflammatory responses. This suggests that cowpox virus encodes several cytokine response modifiers that act together to inhibit the release of pro-inflammatory cytokines in response to infection. These viral countermeasures to host defenses against infection may contribute significantly to the pathology associated with poxvirus infections.
Ray
C A
CA
Department of Microbiology and Immunology, Duke University Medical Center, Durham, North Carolina 27710.
Black
R A
RA
Kronheim
S R
SR
Greenstreet
T A
TA
Sleath
P R
PR
Salvesen
G S
GS
Pickup
D J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D020170:Caspase 1; D002642:Chick Embryo; D015608:Cowpox virus / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D005814:Genes, Viral; D007249:Inflammation / Q000201:enzymology; D007375:Interleukin-1 / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D011499:Protein Processing, Post-Translational; D012697:Serine Endopeptidases / Q000378:metabolism*; D015843:Serpins / Q000235:genetics*; D014764:Viral Proteins; D015678:Viral Structural Proteins / Q000235:genetics
D007375:Interleukin-1; D015843:Serpins; D014764:Viral Proteins; D015678:Viral Structural Proteins; C074641:interleukin-1beta-converting enzyme inhibitor; D012697:Serine Endopeptidases; D020170:Caspase 1; D008666:Metalloendopeptidases