The zinc RING finger of bovine herpesvirus 1-encoded bICP0 protein is crucial for viral replication and virulence

Kazima Saira, Shafiqul Chowdhury, Natasha Gaudreault, Leticia Da Silva, Gail Henderson, Alan Doster, Clinton Jones

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Bovine herpesvirus 1 (BHV-1) infected cell protein 0 (bICP0) stimulates productive infection, in part by activating viral gene expression. The C 3HC4 zinc RING finger of bICP0 is crucial for activating viral transcription and productive infection. In this study, we used a bacterial artificial chromosome containing a wild-type (wt) virulent BHV-1 strain to generate a single amino acid mutation in the C3HC4 zinc RING finger of bICP0. This virus (the 51g mutant) contains a cysteine-to-glycine mutation (51st amino acid) in the C3HC4 zinc RING finger of bICP0. A plasmid expressing the 51g mutant protein did not transactivate viral promoter activity as efficiently as wt bICP0. The 51g mutant virus expressed higher levels of the bICP0 protein than did the 51g rescued virus (51gR) but yielded reduced virus titers following infection of permissive bovine cells. The 51g mutant virus, but not the 51gR virus, grew poorly in bovine cells pretreated with imiquimod to stimulate interferon production. During acute infection of calves, levels of infectious virus were 2 to 3 logs lower in ocular or nasal swabs with 51g than with 51gR. Calves latently infected with the 51g mutant did not reactivate from latency because virus shedding did not occur in ocular or nasal cavities. As expected, calves latently infected with 51gR reactivated from latency following dexamethasone treatment. These studies demonstrate that mutation of a single well-conserved cysteine residue in the C3HC4 zinc RING finger of bICP0 has dramatic effects on the growth properties of BHV-1.

Original languageEnglish (US)
Pages (from-to)12060-12068
Number of pages9
JournalJournal of virology
Volume82
Issue number24
DOIs
StatePublished - Dec 1 2008

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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