Dengue neurovirulence in mice: identification of molecular signatures in the E and NS3 helicase domains.
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.
Bordignon
Juliano
J
Instituto de Biologia Molecular do Paraná/FIOCRUZ, Rua Prof Algacyr Munhoz Máder, Curitiba, Paraná, Brazil.
Strottmann
Daisy M
DM
Mosimann
Ana Luiza P
AL
Probst
Christian M
CM
Stella
Vanessa
V
Noronha
Lucia
L
Zanata
Sílvio M
SM
Dos Santos
Claudia N Duarte
CN
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
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