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A Genetic and Pathologic Study of a DENV2 Clinical Isolate Capable of Inducing Encephalitis and Hematological Disturbances in Immunocompetent Mice

Texto completo
Amorim, Jaime Henrique [1] ; Pereira Bizerra, Raiza Sales [1] ; dos Santos Alves, Rubens Prince [2, 1] ; Sbrogio-Almeida, Maria Elisabete [3] ; Levi, Jose Eduardo [4] ; Capurro, Margareth Lara [5] ; de Souza Ferreira, Luis Carlos [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Microbiol, Vaccine Dev Lab, BR-05508 Sao Paulo - Brazil
[2] Univ Estadual Santa Cruz, Ilheus - Brazil
[3] Butantan Inst, Sao Paulo - Brazil
[4] Univ Sao Paulo, Inst Trop Med, BR-05508 Sao Paulo - Brazil
[5] Univ Sao Paulo, Dept Parasitol, BR-05508 Sao Paulo - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: PLoS One; v. 7, n. 9 SEP 13 2012.
Citações Web of Science: 11

Dengue virus (DENV) is the causative agent of dengue fever (DF), a mosquito-borne illness endemic to tropical and subtropical regions. There is currently no effective drug or vaccine formulation for the prevention of DF and its more severe forms, i.e., dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). There are two generally available experimental models for the study of DENV pathogenicity as well as the evaluation of potential vaccine candidates. The first model consists of non-human primates, which do not develop symptoms but rather a transient viremia. Second, mouse-adapted virus strains or immunocompromised mouse lineages are utilized, which display some of the pathological features of the infection observed in humans but may not be relevant to the results with regard to the wild-type original virus strains or mouse lineages. In this study, we describe a genetic and pathological study of a DENV2 clinical isolate, named JHA1, which is naturally capable of infecting and killing Balb/c mice and reproduces some of the symptoms observed in DENV-infected subjects. Sequence analyses demonstrated that the JHA1 isolate belongs to the American genotype group and carries genetic markers previously associated with neurovirulence in mouse-adapted virus strains. The JHA1 strain was lethal to immunocompetent mice following intracranial (i.c.) inoculation with a LD50 of approximately 50 PFU. Mice infected with the JHA1 strain lost weight and exhibited general tissue damage and hematological disturbances, with similarity to those symptoms observed in infected humans. In addition, it was demonstrated that the JHA1 strain shares immunological determinants with the DENV2 NGC reference strain, as evaluated by cross-reactivity of anti-envelope glycoprotein (domain III) antibodies. The present results indicate that the JHA1 isolate may be a useful tool in the study of DENV pathogenicity and will help in the evaluation of anti-DENV vaccine formulations as well as potential therapeutic approaches. (AU)

Processo FAPESP: 09/50033-7 - Desenvolvimento de vacinas de subunidade contra a dengue baseadas no dominio iii da proteina e e na proteina nao estrutural ns1 recombinantes.
Beneficiário:Jaime Henrique Amorim Santos
Linha de fomento: Bolsas no Brasil - Doutorado