Miller C G, Justus D E, Jayaraman S, Kotwal G J
Department of Microbiology and Immunology, University of Louisville School of Medicine, Kentucky 40292, USA.
Cell Immunol. 1995 May;162(2):326-32. doi: 10.1006/cimm.1995.1086.
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.
痘病毒是一大类非常成功的病原体，可导致人类和其他动物患病。它们编码几种据推测参与逃避宿主免疫的蛋白质，因此是理解病毒感染早期阶段病毒与宿主相互作用的优秀模型。痘苗病毒是痘病毒科中特征最明确的成员，编码一种35 kDa的主要分泌多肽，称为痘苗病毒补体控制蛋白（VCP），其结构与人类和小鼠补体控制蛋白家族相关。补体控制蛋白家族的成员已被证明在体外可抑制补体介导的细菌调理作用以及炎症和吞噬反应的诱导。VCP基因的插入失活导致病毒在体内的毒力减弱。宿主补体在痘病毒感染炎症反应中的作用尚未得到系统研究。在确定VCP在体内炎症反应中的作用之前，我们决定研究宿主补体在病毒感染进程中的作用。我们比较了将主要感染啮齿动物的牛痘病毒注射到同基因小鼠品系B10.D2/nSnJ（C5充足）和B10.D2/oSnJ（C5缺陷）的脚垫中的效果。通过在初次注射后以及再次感染后立即测量特定肿胀反应，并对脚垫染色切片进行组织学检查，宏观监测注射效果。我们的结果表明，两种不同小鼠品系对牛痘病毒感染的初次反应存在显著差异。在B10.D2/oSnJ小鼠脚垫测量中观察到的特定肿胀反应明显更大，持续时间更长，并伴有严重溃疡、水肿、硬结和出血。在3个月后再次注射脚垫，此时肿胀已消退，脚垫已完全恢复到原来的大小和外观，结果显示两个品系之间没有显著差异。这强烈表明宿主补体在对痘病毒感染的初始反应中起重要作用。
