Site-specific alteration of transmissible gastroenteritis virus spike protein results in markedly reduced pathogenicity.
The pathogenicity of neutralization-resistant mutants of the enteric coronavirus transmissible gastroenteritis virus (TGEV) was examined in the newborn piglet. The parental virus (Purdue-115 strain), as well as several mutants selected using monoclonal antibodies (MAbs) directed to antigenic sites A and B, caused an acute enteritis with 100% mortality. By contrast, most of the site D (MAb 40.1) mutants exhibited a strongly reduced enteropathogenicity, leading to the survival of animals inoculated with up to 1000-fold the 100% lethal dose of parental virus. Such a phenotypical change was correlated with point mutations or a small deletion, all located within the S gene sequence coding for the Pro-145 to Cys-155 segment of the mature polypeptide. These observations suggest that an N-terminal subregion of the S molecule is an essential determinant for pathogenesis in TGEV infection.
Bernard
S
S
Laboratoire de Pathologie Porcine, Institut National de la Recherche Agronomique, Nouzilly, France.
Laude
H
H
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005260:Female; D005761:Gastroenteritis, Transmissible, of Swine / Q000821:virology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009500:Neutralization Tests; D011247:Pregnancy; D012367:RNA, Viral; D013552:Swine; D005760:Transmissible gastroenteritis virus / Q000235:genetics / Q000472:pathogenicity*; D014764:Viral Proteins / Q000235:genetics*
D017931:DNA Primers; D012367:RNA, Viral; D014764:Viral Proteins; C064484:spike protein S, Transmissible gastroenteritis virus