Mutation of E1 glycoprotein of classical swine fever virus affects viral virulence in swine

G. R. Risatti, L. G. Holinka, Z. Lu, G. F. Kutish, E. R. Tulman, R. A. French, J. H. Sur, D. L. Rock, M. V. Borca

Research output: Contribution to journalArticlepeer-review

Abstract

Transposon linker insertion mutagenesis of a full-length infectious clone (IC) (pBIC) of the pathogenic classical swine fever virus (CSFV) strain Brescia was used to identify genetic determinants of CSFV virulence and host range. Here, we characterize a virus mutant, RB-C22v, possessing a 19-residue insertion at the carboxyl terminus of E1 glycoprotein. Although RB-C22v exhibited normal growth characteristics in primary porcine macrophage cell cultures, the major target cell of CSFV in vivo, it was markedly attenuated in swine. All RB-C22v-infected pigs survived infection remaining clinically normal in contrast to the 100% mortality observed for BICv-infected animals. Comparative pathogenesis studies demonstrated a delay in RB-C22v spread to, and decreased replication in the tonsils, a 102 to 107 log10 reduction in virus titers in lymphoid tissues and blood, and an overall delay in generalization of infection relative to BICv. Notably, RB-C22v-infected animals were protected from clinical disease when challenged with pathogenic BICv at 3, 5, 7, and 21 days post-RB-C22v inoculation. Viremia, viral replication in tissues, and oronasal shedding were reduced in animals challenged at 7 and 21 DPI. Notably BICv-specific RNA was not detected in tonsils of challenged animals. These results indicate that a carboxyl-terminal domain of E1 glycoprotein affects virulence of CSFV in swine, and they demonstrate that mutation of this domain provides the basis for a rationally designed and efficacious live-attenuated CSF vaccine.

Original languageEnglish (US)
Pages (from-to)116-127
Number of pages12
JournalVirology
Volume343
Issue number1
DOIs
StatePublished - Dec 5 2005

Keywords

  • Attenuation
  • CSFV
  • Glycoproteins
  • Mutagenesis
  • Pathogenesis
  • Protection
  • Transposon
  • Vaccine
  • Virulence

ASJC Scopus subject areas

  • Virology

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