Poxvirus-induced alteration of arachidonate metabolism.
Recent evidence suggests that orthopoxviruses have an obligate requirement for arachidonic acid metabolites during replication in vivo and in vitro. Our report indicates that a virus family (Poxviridae) possesses multiple genes that function to regulate arachidonate metabolism. Analyses of BS-C-1 cells infected with cowpox virus or vaccinia virus detected enhanced arachidonate product formation from both the cyclooxygenase (specifically prostaglandins E2 and F2 alpha) and lipoxygenase (specifically 15-hydroxyeicosatetraenoic acid and 12-hydroxyeicosatetraenoic acid) pathways. In contrast, human parainfluenza type 3 or herpes simplex virus type 1 infections did not increase arachidonate metabolism. Results were consistent with a virus early-gene product either directly mediating or inducing a host factor that mediated the up-regulation of arachidonate metabolism, although vaccinia growth factor was not responsible. In addition, the cowpox virus 38-kDa protein-encoding gene, which is associated with inhibition of an inflammatory response, correlated with inhibition of formation of a product biochemically characteristic of (14R,15S)-dihydroxyeicosatetraenoic acid. We propose that orthopoxvirus-induced up-regulation of arachidonic acid metabolism during infection renders the infected cells susceptible to generation of inflammatory mediators from both the cyclooxygenase and the lipoxygenase pathways, and poxviruses, therefore, possess at least one gene (38K) that can alter the lipoxygenase-metabolite spectrum.
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
G J
GJ
Palumbo
W C
WC
Glasgow
R M
RM
Buller
D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D002851:Chromatography, High Pressure Liquid; D015605:Cowpox / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D006367:HeLa Cells; D006561:Herpes Simplex / Q000378:metabolism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D018108:Respirovirus / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors; D014764:Viral Proteins / Q000378:metabolism
D006893:Hydroxyeicosatetraenoic Acids; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014764:Viral Proteins; C051087:vaccinia growth factor; D016718:Arachidonic Acid; D003513:Cycloheximide; D001093:Arachidonate 15-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases