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    • 6. 发明授权
    • VACCINE AGAINST ROTAVIRUS INFECTION COMPRISING PEPTIDES OF VIRAL ENTEROTOXIN NSP4
    • 轮状病毒疫苗感染VIRALENTEROTOXINES NSP4的含肽
    • EP0833670B1
    • 2003-09-03
    • EP96923329.5
    • 1996-06-14
    • BAYLOR COLLEGE OF MEDICINE
    • ESTES, Mary, K.BALL, JudithTIANG, Peng
    • A61K38/16A61K39/15A61P43/00
    • C07K14/005A61K38/00A61K39/00A61K49/0004C07K16/10C12N2720/12322
    • The rotavirus nonstructural glycoprotein, NSP4, performs multiple functions in the virus replication cycle, especially during viral morphogenesis. Specifically, NSP4 is an intracellular receptor that mediates the acquisition of a transient membrane envelope during the budding of newly formed subviral particles into the endoplasmic reticulum (ER). We now report that NSP4 alone induces diarrhea in young (6-11 days) rodents (mice and rats) when administered by the intraperitoneal (IP) or intraileal (IL) route. A 22 amino acid synthetic peptide corresponding to NSP4 residues 114-135 (NSP4 114-135) also induces diarrheal disease. Disease induction by the protein or peptide is specific and is both age and dose-dependent, and it occurs in the absence of virus replication. No diarrhea was observed with control proteins or peptides administered to the same age animals and by the same route. Electrophysiologic data from intestinal mucosa indicate that NSP4 and the peptide stimulate a calcium-mediated rise in chloride secretion, i.e., potentiate chloride secretion by a calcium dependent signaling pathway. Based on these results, a new mechanism by which rotavirus induces diarrhea is proposed. This model involves two intestinal receptors. One receptor is needed to permit viral infection to be initiated, while a second age-dependent receptor is needed to interact with NSP4, a noncapsid viral protein, expressed and released from viral-infected cells. Induction of a signal transduction pathway following the interaction of NSP4 (a viral enterotoxin) with the second receptor leads to chloride secretion and diarrhea, i.e., diarrhea is induced when NSP4, acting as a viral enterotoxin, triggers a signal transduction pathway. The action of this viral enterotoxin with its specific receptor mimics that of bacterial enterotoxins.
    • 10. 发明公开
    • ROTAVIRUS ENTEROTOXIN NSP4 AND METHODS OF USING SAME
    • NSP4轮状病毒肠毒素及其制备方法
    • EP0833670A2
    • 1998-04-08
    • EP96923329.0
    • 1996-06-14
    • BAYLOR COLLEGE OF MEDICINE
    • ESTES, Mary, K.BALL, JudithTIANG, Peng
    • C12N15A61K39A61K45A61K49A61P1A61P3A61P31C07K14C07K16C12N7C12P21C12Q1G01N33A61K38
    • C07K14/005A61K38/00A61K39/00A61K49/0004C07K16/10C12N2720/12322
    • The rotavirus nonstructural glycoprotein, NSP4, performs multiple functions in the virus replication cycle, especially during viral morphogenesis. Specifically, NSP4 is an intracellular receptor that mediates the acquisition of a transient membrane envelope during the budding of newly formed subviral particles into the endoplasmic reticulum (ER). We now report that NSP4 alone induces diarrhea in young (6-11 days) rodents (mice and rats) when administered by the intraperitoneal (IP) or intraileal (IL) route. A 22 amino acid synthetic peptide corresponding to NSP4 residues 114-135 (NSP4 114-135) also induces diarrheal disease. Disease induction by the protein or peptide is specific and is both age and dose-dependent, and it occurs in the absence of virus replication. No diarrhea was observed with control proteins or peptides administered to the same age animals and by the same route. Electrophysiologic data from intestinal mucosa indicate that NSP4 and the peptide stimulate a calcium-mediated rise in chloride secretion, i.e., potentiate chloride secretion by a calcium dependent signaling pathway. Based on these results, a new mechanism by which rotavirus induces diarrhea is proposed. This model involves two intestinal receptors. One receptor is needed to permit viral infection to be initiated, while a second age-dependent receptor is needed to interact with NSP4, a noncapsid viral protein, expressed and released from viral-infected cells. Induction of a signal transduction pathway following the interaction of NSP4 (a viral enterotoxin) with the second receptor leads to chloride secretion and diarrhea, i.e., diarrhea is induced when NSP4, acting as a viral enterotoxin, triggers a signal transduction pathway. The action of this viral enterotoxin with its specific receptor mimics that of bacterial enterotoxins.