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Dengue neurovirulence in mice: Identification of molecular signatures in the E and NS3 helicase domains

✍ Scribed by Juliano Bordignon; Daisy M. Strottmann; Ana Luiza P. Mosimann; Christian M. Probst; Vanessa Stella; Lucia Noronha; Sílvio M. Zanata; Claudia N. Duarte dos Santos

Book ID: 102384794
Publisher: John Wiley and Sons
Year: 2007
Tongue: English
Weight: 378 KB
Volume: 79
Category: Article
ISSN: 0146-6615
DOI: 10.1002/jmv.20958

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✦ Synopsis

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. J. Med. Virol. 79:1506–1517, 2007. © Wiley‐Liss, Inc.

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