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filingDate 2007-05-29-04:00^^<http://www.w3.org/2001/XMLSchema#date>
grantDate 2014-09-22-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationDate 2014-09-22-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber KR-101432840-B1
titleOfInvention New pathogenic determinants in the E2 structural glycoprotein of porcine cholera virus
abstract Porcine cholera virus (CSFV) E2 glycoprotein is a major inducer of neutralizing antibodies and protective immunity in pigs. E2 mediates virus adsorption in the target cell and contains genetic determinants associated with viral pathogenicity. CSFV E2 is also known to be associated with residues 829 to 837, recognized by the monoclonal antibody (mAb) WH303 used to differentiate CSFV from the associated pestiviruses, bovine viral diarrhea virus (BVDV) and borderline virus And a distinct epitope (TAVSPTTLR). In this study, a CSFV infectious clone of the pathogenic Brescia isolate (BICv) was used to progressively mutate the mAb WH303 epitope of CSFV E2 to the homologous amino acid sequence of BVDV strain NADL E2 (TSFNMDTLA). The mutant T4v (TSFNMDTLR) and T5v (TSFNMDTLA) showed similar in vitro growth characteristics to those of the maternal BICv, whereas the viral mutants T1v (TSFSPTTLR), T2v (TSFNPTTLR) and T3v (TSFNMTTLR) 10 - fold decrease in virus yield and significant decrease in plaque size. Immunocytochemical reactivity with WH303 disappeared only in T3v, T4v and T5v. Interestingly, the progressive mutation of the WH303 epitope had additional effects on virus attenuation in pigs, with the mutant T1v, T2v or T3v progressively weaker but still invariably leading to lethal CSF, and T4v only mild and transient clinical And T5v did not induce disease. Pigs infected with T4v or T5v exhibited a significant reduction in viral replication, and viral release, in the tonsil, draining lymph nodes, spleen and kidneys. As a result, animals infected with T5v were protected from clinical disease on immunological testing with pathogenic Brescia virus on days 3 or 21 after T5v inoculation. These results indicate that amino acid residues 830 to 834 of E2 are crucial for the virulence of CSFV in pigs and that engineering at these gene locations can provide a basis for live-attenuated CSF vaccines that are reasonably designed.
priorityDate 2006-05-30-04:00^^<http://www.w3.org/2001/XMLSchema#date>
type http://data.epo.org/linked-data/def/patent/Publication

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