title: Severe and prolonged inflammatory response to localized cowpox virus infection in footpads of C5-deficient mice: investigation of the role of host complement in poxvirus pathogenesis.
abstract: Poxviruses are a large, complex group of highly successful pathogens that cause disease in humans and other animals. They encode several proteins postulated to be involved in the evasion of host immunity and therefore serve as excellent models for understanding virus-host interaction during the early stages of viral infection. Vaccinia virus, the best characterized member of the poxviridae family, encodes a 35-kDa major secretory polypeptide termed vaccinia virus complement control protein (VCP), which is structurally related to the family of human and mouse complement control proteins. Members of the family of complement control proteins have been shown to inhibit complement-mediated opsonization of bacteria and induction of inflammatory and phagocytic responses in vitro. Insertional inactivation of the VCP gene results in attenuation of viral virulence in vivo. The role of host complement in the inflammatory response to poxvirus infection has not been systematically investigated. Prior to determining the role of VCP on inflammatory responses in vivo, we decided to investigate the role of host complement in the progression of viral infection. We have compared the effects of injection of cowpox virus, primarily a rodent virus, into footpads of congenic mice strains B10.D2/nSnJ (C5-sufficient) and B10.D2/oSnJ (C5-deficient). The effects of the injection were monitored macroscopically by measuring the specific swelling response immediately following primary injection and subsequently after reinfection and by histological examination of the stained sections of the footpads. Our results indicate that there is a significant variation in the primary response in the two different mouse strains to cowpox virus infection. The specific swelling response observed in measurements from the footpads of the B10.D2/oSnJ mice was significantly greater, persisted for a longer duration, and was accompanied by severe ulceration, edema, induration, and hemorrhaging. Reinjection of the footpads after a 3-month period, during which time the swelling had subsided and the footpad had fully recovered to its original size and appearance, showed no significant differences between the two strains. This strongly suggests that the host complement plays a significant role during the initial response to poxvirus infection.
authors.affiliation: Department of Microbiology and Immunology, University of Louisville School of Medicine, Kentucky 40292, USA.
authors.forename: C G
authors.initials: CG
authors.lastname: Miller
authors.forename: D E
authors.initials: DE
authors.lastname: Justus
authors.forename: S
authors.initials: S
authors.lastname: Jayaraman
authors.forename: G J
authors.initials: GJ
authors.lastname: Kotwal
mesh_terms: D000818:Animals; D003182:Complement C5 / Q000172:deficiency*; D015605:Cowpox / Q000276:immunology* / Q000473:pathology; D015608:Cowpox virus / Q000472:pathogenicity*; D005260:Female; D005528:Foot; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D003182:Complement C5