Multigenic evasion of inflammation by poxviruses

• Published in: Journal of Virology 1994-03, Vol.68 (3), p.1737-1749
• Main Authors: PALUMBO, G. J, BULLER, R. M, GLASGOW, W. C
• Format: Article
• Language: English
• Subjects: acide arachidonique; acido araquidonico; Allantois - microbiology; Allantois - pathology; animal viruses; Animals; arachidonic acid; Arachidonic Acid - metabolism; Biological and medical sciences; Cell Line; Cercopithecus aethiops; Chick Embryo; chicks; Chorion - microbiology; Chorion - pathology; cowpox virus; Cowpox virus - genetics; Cowpox virus - growth & development; Cowpox virus - pathogenicity; Cytopathogenic Effect, Viral - drug effects; Cytopathogenic Effect, Viral - genetics; foetal membranes; Fundamental and applied biological sciences. Psychology; Genes, Viral; inflamacion; inflammation; Inflammation - microbiology; inhibicion; inhibition; Kidney - cytology; Leukotrienes - biosynthesis; lipid metabolism; membranas fetales; membrane foetale; metabolisme des lipides; metabolismo de lipidos; Microbiology; mutant; mutantes; mutants; orthopoxvirus; Orthopoxvirus - genetics; Orthopoxvirus - growth & development; Orthopoxvirus - pathogenicity; pathogenese; pathogenesis; patogenesis; pollito; poussin; proteinas; proteine; proteins; Replicative cycle, interference, host-virus relations, pathogenicity, miscellaneous strains; Serpins - genetics; Serpins - pharmacology; Vaccinia virus - growth & development; Vaccinia virus - metabolism; Vaccinia virus - pathogenicity; Viral Proteins; Virology; Virulence - genetics; virus de los animales; virus des animaux
• ISSN: 0022-538X; 1098-5514
• DOI: 10.1128/jvi.68.3.1737-1749.1994

Analyses of different cowpox virus (Brighton Red strain [CPV-BR]) mutants indicate that there is a minimum of three genes encoded by CPV-BR that are nonessential for virus replication in tissue culture but are involved in inhibiting the generation of an inflammatory response in the chicken embryo chorioallantoic membrane (CAM) model. The CPV-BR-encoded anti-inflammatory genes include the gene encoding the 38-kDa protein (also called 38K, crmA, SPI-2, or VV-WR-ORF-B13R), a tumor necrosis factor receptor homolog, and an unidentified gene that maps to the right end of the CPV genome. The kinetics of triggering of an inflammatory response at the site of virus infection as well as the magnitude of the response is dependent on the virus-encoded inhibitor that is deleted. Virus yields recovered from pocks decreased in proportion to the magnitude of the inflammatory response. The deletion of these identified inhibitors of inflammation was associated with attenuation of the mutant viruses in mice. These data confirm the existence of multiple poxvirus-encoded host defense modifiers whose function is to block the generation of an inflammatory response at the site of virus infection, which allows enhanced virus replication and potentially facilitates virus transmission.