Kapadia Sharookh B, Levine Beth, Speck Samuel H, Virgin Herbert W
Department of Immunology and Pathology, Department of Molecular Microbiology, Washington University School of Medicine, Box 8118, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Immunity. 2002 Aug;17(2):143-55. doi: 10.1016/s1074-7613(02)00369-2.
Several gamma-herpesviruses encode homologs of host regulators of complement activation (RCA) proteins, suggesting that they have evolved immune evasion strategies targeting complement. We evaluated the role of complement factor C3 (C3) and the murine gamma-herpesvirus 68 (gammaHV68) RCA protein in viral pathogenesis. Deletion of the gammaHV68 RCA protein decreased virulence during acute CNS infection, and this attenuation was specifically reversed by deletion of host C3. The gammaHV68 RCA protein was also important for persistent viral replication and virulence in IFNgammaR(-/-) mice. In addition, C3 played a role in regulating latency, but this was not counteracted by the gammaHV68 RCA protein. We conclude that complement is a key host defense against gamma-herpesvirus infection and that gamma-herpesviruses have evolved an immune evasion strategy that is effective against complement-mediated antiviral responses during acute but not latent infection.
几种γ-疱疹病毒编码补体激活宿主调节因子（RCA）蛋白的同源物，这表明它们已经进化出针对补体的免疫逃避策略。我们评估了补体因子C3（C3）和鼠γ-疱疹病毒68（γHV68）RCA蛋白在病毒发病机制中的作用。γHV68 RCA蛋白的缺失降低了急性中枢神经系统感染期间的毒力，而宿主C3的缺失可特异性逆转这种减弱。γHV68 RCA蛋白对于IFNγR（-/-）小鼠中的持续性病毒复制和毒力也很重要。此外，C3在调节潜伏期方面发挥作用，但这并未被γHV68 RCA蛋白抵消。我们得出结论，补体是宿主抵抗γ-疱疹病毒感染的关键防御机制，并且γ-疱疹病毒已经进化出一种免疫逃避策略，该策略在急性感染而非潜伏感染期间对补体介导的抗病毒反应有效。
