MHV68 complement regulatory protein facilitates MHV68 replication in primary macrophages in a complement independent manner

Vera L. Tarakanova, Jerome M. Molleston, Megan Goodwin, Herbert W. Virgin IV

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish
Pages (from-to)323-328
Number of pages6
JournalVirology
Volume396
Issue number2
DOIs
StatePublished - Jan 20 2010

Keywords

  • Complement
  • Gammaherpesvirus
  • MHV68
  • Viral RCA

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