101. Determinants in the envelope E protein and viral RNA helicase NS3 that influence the induction of apoptosis in response to infection with dengue type 1 virus.
- Author
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Duarte dos Santos CN, Frenkiel MP, Courageot MP, Rocha CF, Vazeille-Falcoz MC, Wien MW, Rey FA, Deubel V, and Desprès P
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, Cell Line, Chlorocebus aethiops, Culicidae, Dengue Virus enzymology, Dengue Virus genetics, Dengue Virus growth & development, Epithelial Cells pathology, Epithelial Cells virology, Glycoproteins metabolism, Humans, Kinetics, Membrane Fusion, Models, Molecular, Molecular Sequence Data, Mutation genetics, Neurons pathology, Neurons virology, Protein Conformation, Protein Processing, Post-Translational, RNA Helicases genetics, RNA, Viral biosynthesis, Viral Envelope Proteins genetics, Viral Proteins biosynthesis, Viral Proteins metabolism, Virulence, Virus Replication, Apoptosis, Dengue Virus pathogenicity, RNA Helicases chemistry, RNA Helicases metabolism, Viral Envelope Proteins chemistry, Viral Envelope Proteins metabolism
- Abstract
One mechanism by which dengue (DEN) virus may cause cell death is apoptosis. In this study, we investigated whether the genetic determinants responsible for acquisition by DEN type 1 (DEN-1) virus of mouse neurovirulence interfere with the induction of apoptosis. Neurovirulent variant FGA/NA d1d was generated during the adaptation of the human isolate of DEN-1 virus strain FGA/89 to grow in newborn mouse brains and mosquito cells in vitro [Desprès, P. Frenkiel, M. -P. Ceccaldi, P.-E. Duarte Dos Santos, C. and Deubel, V. (1998) J. Virol., 72: 823-829]. Genetic determinants possibly responsible for mouse neurovirulence were studied by sequencing the entire genomes of both DEN-1 viruses. Three amino acid differences in the envelope E protein and one in the nonstructural NS3 protein were found. The cytotoxicity of the mouse-neurovirulent DEN-1 variant was studied in different target cells in vitro and compared with the parental strain. FGA/NA d1d was more pathogenic for mouse neuroblastoma cells and attenuated for human hepatoma cells. Changes in virus replicative functions and virus assembly may account, in a large part, for the differences in the induction of apoptosis. Our data suggest that identified amino acid substitutions in the envelope E protein and viral RNA helicase NS3 may influence DEN-1 virus pathogenicity by altering viral growth., (Copyright 2000 Academic Press.)
- Published
- 2000
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