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Site-specific alteration of transmissible gastroenteritis virus spike protein results in markedly reduced pathogenicity

Serge Bernard^1,

¹ Laboratoire de Pathologie Porcine, Institut National de la Recherche Agronomique, Nouzilly
and² Unité de Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, Jouy-en-Josas, France

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.

^* Author for correspondence. Fax +33 1 34 65 26 21. e-mail laude@biotec.jouy.inra.fr

Present address: Unité de Pathologie Infectieuse Immunologie, Institut National de la Recherche Agronomique, Nouzilly, France.

Received 13 January 1995; accepted 10 May 1995.

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