title: Dengue neurovirulence in mice: identification of molecular signatures in the E and NS3 helicase domains.
abstract: Recent observations indicate that the clinical profile of dengue virus (DENV) infection is changing, and that neurological manifestations are becoming frequent. The neuro pathogenesis of dengue, and the contribution of viral and host factors to the disease are not well understood. To define the amino acid substitutions in DENV potentially implicated in the acquisition of a neurovirulent phenotype we used a murine model to characterize two neuroadapted strains of DENV-1, FGA/NA a5c (previously obtained), and FGA/NA P6 (recently obtained). Only three amino acid substitutions were identified in the neurovirulent strains, mapping to the E and NS3 helicase domains. These mutations enhanced the ability of neuroadapted viral strains to replicate in the CNS of infected mice, causing extensive damage with leptomeningitis and encephalitis.
authors: Instituto de Biologia Molecular do Paraná/FIOCRUZ, Rua Prof Algacyr Munhoz Máder, Curitiba, Paraná, Brazil.
authors: Juliano
authors: J
authors: Bordignon
authors: Daisy M
authors: DM
authors: Strottmann
authors: Ana Luiza P
authors: AL
authors: Mosimann
authors: Christian M
authors: CM
authors: Probst
authors: Vanessa
authors: V
authors: Stella
authors: Lucia
authors: L
authors: Noronha
authors: Sílvio M
authors: SM
authors: Zanata
authors: Claudia N Duarte
authors: CN
authors: Dos Santos
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003715:Dengue / Q000821:virology*; D003716:Dengue Virus / Q000235:genetics / Q000472:pathogenicity*; D051379:Mice; D008958:Models, Molecular; D009420:Nervous System / Q000821:virology; D009474:Neurons; D017354:Point Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D020365:RNA Helicases / Q000737:chemistry / Q000235:genetics; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics*; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics*; D014774:Virulence / Q000235:genetics; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D020365:RNA Helicases; D012697:Serine Endopeptidases; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C060028:NS3 protein, flavivirus; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C072281:E protein TH Sman, Dengue virus