title: Identification of a novel virulence determinant within the E2 structural glycoprotein of classical swine fever virus.
abstract: Classical swine fever virus (CSFV) E2 glycoprotein contains a discrete epitope (TAVSPTTLR, residues 829-837 of CSFV polyprotein) recognized by monoclonal antibody (mAb) WH303, used to differentiate CSFV from related ruminant pestiviruses, Bovine Viral Diarrhea Virus (BVDV) and Border Disease Virus (BDV), that infect swine without causing disease. Progressive mutations were introduced into mAb WH303 epitope in CSFV virulent strain Brescia (BICv) to obtain the homologous amino acid sequence of BVDV strain NADL E2 (TSFNMDTLA). In vitro growth of mutants T1v (TSFSPTTLR), T2v (TSFNPTTLR), T3v (TSFNMTTLR) was similar to parental BICv, while mutants T4v (TSFNMDTLR) and T5v (TSFNMDTLA) exhibited a 10-fold decrease in virus yield and reduced plaque size. In vivo, T1v, T2v or T3v induced lethal disease, T4v induced mild and transient disease and T5v induced mild clinical signs. Protection against BICv challenge was observed at 3 and 21 days post-T5v infection. These results indicate that E2 residues TAVSPTTLR play a significant role in CSFV virulence.
authors.affiliation: Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USA. guillermo.risatti@uconn.edu
authors.forename: G R
authors.initials: GR
authors.lastname: Risatti
authors.forename: L G
authors.initials: LG
authors.lastname: Holinka
authors.forename: C
authors.initials: C
authors.lastname: Carrillo
authors.forename: G F
authors.initials: GF
authors.lastname: Kutish
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.forename: E R
authors.initials: ER
authors.lastname: Tulman
authors.forename: I Fernandez
authors.initials: IF
authors.lastname: Sainz
authors.forename: M V
authors.initials: MV
authors.lastname: Borca
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D006691:Classical Swine Fever / Q000503:physiopathology / Q000821:virology; D006692:Classical Swine Fever Virus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D000939:Epitopes / Q000235:genetics; D005814:Genes, Viral; D016297:Mutagenesis, Site-Directed; D020125:Mutation, Missense; D016019:Survival Analysis; D013552:Swine; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D010948:Viral Plaque Assay; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
chemical_list: D000939:Epitopes; D014759:Viral Envelope Proteins; C087086:glycoprotein E2, classical swine fever virus