{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:33:32Z","timestamp":1791297212863,"version":"4.1.0"},"reference-count":47,"publisher":"Microbiology Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,10,1]]},"abstract":"<jats:p>The induction of apoptotic cell death is a prominent cytopathic effect of dengue (DEN) viruses. One of the key questions to be addressed is which viral components induce apoptosis in DEN virus-infected cells. This study investigated whether the small membrane (M) protein was involved in the induction of apoptosis by DEN virus. This was addressed by using a series of enhanced green fluorescent protein-fused DEN proteins. Evidence is provided that intracellular production of the M ectodomains (residues M-1 to M-40) of all four DEN serotypes triggered apoptosis in host cells such as mouse neuroblastoma Neuro 2a and human hepatoma HepG2 cells. The M ectodomains of the wild-type strains of Japanese encephalitis, West Nile and yellow fever viruses also had proapoptotic properties. The export of the M ectodomain from the Golgi apparatus to the plasma membrane appeared to be essential for the initiation of apoptosis. The study found that anti-apoptosis protein Bcl-2 protected HepG2 cells against the death-promoting activity of the DEN M ectodomain. This suggests that the M ectodomain exerts its cytotoxic effects by activating a mitochondrial apoptotic pathway. The cytotoxicity of the DEN M ectodomain reflected the intrinsic proapoptotic properties of the nine carboxy-terminal amino acids (residues M-32 to M-40) designated<jats:italic>ApoptoM<\/jats:italic>. Residue M-36 was unique in that it modulated the death-promoting activity of the M ectodomain. Defining the<jats:italic>ApoptoM<\/jats:italic>-activated signalling pathways leading to apoptosis will provide the basis for studying how the M protein might play a key role in the fate of the flavivirus-infected cells.<\/jats:p>","DOI":"10.1099\/vir.0.19163-0","type":"journal-article","created":{"date-parts":[[2003,9,18]],"date-time":"2003-09-18T03:18:12Z","timestamp":1063855092000},"page":"2781-2793","source":"Crossref","is-referenced-by-count":80,"title":["Dengue virus M protein contains a proapoptotic sequence referred to as ApoptoM"],"prefix":"10.1099","volume":"84","author":[{"given":"Adeline","family":"Catteau","sequence":"first","affiliation":[{"name":"Unit\u00e9 Postulante des Interactions Mol\u00e9culaires Flavivirus-H\u00f4tes, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Kalinina","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Postulante des Interactions Mol\u00e9culaires Flavivirus-H\u00f4tes, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Wagner","sequence":"additional","affiliation":[{"name":"Plate-Forme de Cytom\u00e9trie, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Deubel","sequence":"additional","affiliation":[{"name":"Unit\u00e9 de Biologie des Infections Virales Emergentes, Institut Pasteur, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Pierre","family":"Courageot","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Postulante des Interactions Mol\u00e9culaires Flavivirus-H\u00f4tes, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Despr\u00e8s","sequence":"additional","affiliation":[{"name":"Unit\u00e9 Postulante des Interactions Mol\u00e9culaires Flavivirus-H\u00f4tes, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"345","reference":[{"key":"R1","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/S0968-0004(00)01740-0","article-title":"Life-or-death decisions by the Bcl-2 protein family","volume":"26","author":"Adams","year":"2001","journal-title":"Trends Biochem Sci"},{"key":"R2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/0042-6822(91)90809-P","article-title":"Dengue virus premembrane and membrane proteins elicit a protective immune response","volume":"185","author":"Bray","year":"1991","journal-title":"Virology"},{"key":"R3","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1002\/(SICI)1097-4652(199911)181:2<231::AID-JCP5>3.0.CO;2-L","article-title":"The p53 pathway and apoptosis","volume":"181","author":"Burns","year":"1999","journal-title":"J Cell Physiol"},{"key":"R4","article-title":"Flaviviruses and apoptosis regulation","volume-title":"In Viruses and Apoptosis . 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