Critical role of complement and viral evasion of complement in acute, persistent, and latent gamma-herpesvirus infection

Immunity. 2002 Aug;17(2):143-55. doi: 10.1016/s1074-7613(02)00369-2.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Animals
  • Brain / pathology
  • Brain / virology
  • Cell Line
  • Cells, Cultured
  • Chronic Disease
  • Complement C3 / genetics
  • Complement C3 / immunology*
  • Complement Factor B / genetics
  • Complement Factor B / immunology*
  • Female
  • Fibroblasts / cytology
  • Herpesviridae Infections / immunology*
  • Herpesviridae Infections / pathology
  • Herpesviridae Infections / virology
  • Immunocompromised Host
  • Lung / pathology
  • Lung / virology
  • Male
  • Meningoencephalitis / immunology*
  • Meningoencephalitis / pathology
  • Meningoencephalitis / virology
  • Mice
  • Mice, Inbred C57BL
  • Open Reading Frames
  • Receptors, Interferon / genetics
  • Rhadinovirus / growth & development
  • Rhadinovirus / immunology*
  • Rhadinovirus / pathogenicity
  • Rhadinovirus / physiology
  • Viral Proteins / genetics
  • Viral Proteins / immunology*
  • Viral Proteins / physiology
  • Virulence
  • Virus Latency / immunology*
  • Virus Replication

Substances

  • Complement C3
  • Receptors, Interferon
  • Viral Proteins
  • interferon gamma receptor
  • Complement Factor B