Critical role of complement and viral evasion of complement in acute, persistent, and latent gamma-herpesvirus infection.
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.
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.
Sharookh B
SB
Kapadia
Beth
B
Levine
Samuel H
SH
Speck
Herbert W
HW
Virgin
D000208:Acute Disease; D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D002908:Chronic Disease; D003176:Complement C3 / Q000235:genetics / Q000276:immunology*; D011415:Complement Factor B / Q000235:genetics / Q000276:immunology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016867:Immunocompromised Host; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D008590:Meningoencephalitis / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D016366:Open Reading Frames; D017471:Receptors, Interferon / Q000235:genetics; D018144:Rhadinovirus / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D014774:Virulence; D017735:Virus Latency / Q000276:immunology*; D014779:Virus Replication; D000096743:Interferon gamma Receptor
D003176:Complement C3; D011415:Complement Factor B; D017471:Receptors, Interferon; D014764:Viral Proteins; D000096743:Interferon gamma Receptor