SEVERE AND PROLONGED INFLAMMATORY RESPONSE TO LOCALIZED COWPOX VIRUS-INFECTION IN FOOTPADS OF C5-DEFICIENT MICE - INVESTIGATION OF THE ROLEOF HOST COMPLEMENT IN POXVIRUS PATHOGENESIS

Poxviruses are a large, complex group of highly successful pathogens t hat cause disease in humans and other animals. They encode several pro teins postulated to be involved in the evasion of host immunity and th erefore serve as excellent models for understanding virus-host interac tion during the early stages of viral infection, Vaccinia virus, the b est characterized member of the poxviridae family, encodes a 35-kDa ma jor secretory polypeptide termed vaccinia virus complement control pro tein (VCP), which is structurally related to the family of human and m ouse complement control proteins, Members of the family of complement control proteins have been shown to inhibit complement-mediated opsoni zation of bacteria and induction of inflammatory and phagocytic respon ses in vitro. Insertional inactivation of the VCP gene results in atte nuation of viral virulence in vivo. The role of host complement in the inflammatory response to poxvirus infection has not been systematical ly investigated. Prior to determining the role of VCP on inflammatory responses in vivo, we decided to investigate the role of host compleme nt 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 macroscopi cally by measuring the specific swelling response immediately followin g primary injection and subsequently after reinfection and by histolog ical 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 spe cific 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 full y 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 t o poxvirus infection. (C) 1995 academic Press, Inc.