title: MHV68 complement regulatory protein facilitates MHV68 replication in primary macrophages in a complement independent manner.
abstract: Murine gammaherpesvirus-68 (MHV68) is genetically related to human Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus and provides a tractable model to study gammaherpesvirus-host interactions in vivo and in vitro. The MHV68-encoded v-RCA product inhibits murine complement activation and shares sequence homology with other virus and host regulators of complement activation. Here we show that v-RCA is required for efficient MHV68 replication in primary murine macrophages, but not in murine embryonic fibroblasts. v-RCA-deficient MHV68 mutant viruses display defects in viral DNA synthesis in infected macrophages. Importantly, attenuated growth of v-RCA mutant viruses is not rescued in macrophages lacking critical components of the complement system including C3, indicating that the macrophage-specific role of v-RCA in MHV68 replication is complement-independent. This contrasts with the situation in vivo in which attenuated neurovirulence of v-RCA mutant viruses is rescued in C3-deficient mice. This study shows a novel, complement independent cell-type-specific function of a gammaherpesvirus RCA protein.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. vera@mcw.edu
authors.forename: Vera L
authors.initials: VL
authors.lastname: Tarakanova
authors.forename: Jerome M
authors.initials: JM
authors.lastname: Molleston
authors.forename: Megan
authors.initials: M
authors.lastname: Goodwin
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D000818:Animals; D002460:Cell Line; D003167:Complement Activation / Q000502:physiology*; D003176:Complement C3 / Q000502:physiology; D004279:DNA, Viral / Q000096:biosynthesis; D005347:Fibroblasts / Q000821:virology; D018142:Gammaherpesvirinae / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008264:Macrophages / Q000821:virology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014779:Virus Replication / Q000502:physiology*
chemical_list: D003176:Complement C3; D004279:DNA, Viral