IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Role of N-Glycosylation of Dengue Virus Envelope Protein
Autor/es:
ANDREA GAMARNIK, JUAN MONDOTTE, PIERRE-YVES LOZACH AND ALI AMARA
Lugar:
Washington, USA
Reunión:
Simposio; 8th International Symposium on POsitive Strand RNA Viruses; 2007
Resumen:
Role of N-Glycosylation of Dengue Virus Envelope Protein Andrea Gamarnik1, Juan Mondotte1, Pierre-Yves Lozach2, and Ali Amara2 1Fundación Instituto Leloir, Buenos Aires Argentina. 2Pasteur Institute, Paris, France Dengue virus, a member of the flavivirus genus, is the most prevalent cause of arthropod-borne viral illness in humans. The viral envelope protein (E) contains two N-linked glycosylation sites at Asn-67 and Asn-153. The glycosylation site at position 153 is conserved in most flaviviruses, while the position 67 is unique for dengue viruses. N-linked oligosaccharide side chains on flavivirus E proteins have been associated with viral morphogenesis, infectivity, and tropism. Here, we examined the relevance of each N-linked glycan on dengue virus 2 E protein by removing these sites in the context of infectious viral particles. We found that both potential glycosylation sites of dengue virus E protein are utilized in mammalian and mosquito cells. Using a novel dengue virus reporter system carrying a luciferase gene in the context of the full-length genome, we found that viral particles lacking Asn-67 were able to infect mammalian cells, translate and replicate the viral genome, but production of viral progeny was abolished. In addition, the glycan at position 153 modestly increased viral particle production but dramatically increased viral infectivity in mammalian cells. In contrast, ablation of one or both glycosylation sites in the context of a dengue virus infectious clone yielded viruses that replicate and propagate in mosquito cells. In summary, our results demonstrate a crucial role of N-glycosylation of dengue virus E protein during viral morphogenesis in mammalian but not in mosquito cells, highlighting the involvement of distinct host functions during dengue virus replication.