Development of a model of Saint Louis encephalitis infection and disease in mice.
Flaviviruses are a genre of closely related viral pathogens which emerged in the last decades in Brazil and in the world. Saint (St.) Louis encephalitis virus (SLEV) is a neglected flavivirus that can cause a severe neurological disease that may lead to death or sequelae. St. Louis encephalitis pathogenesis is poorly understood, which hinders the development of specific treatment or vaccine.



To address this problem, we developed a model of SLEV infection in mice to study mechanisms involved in the pathogenesis of severe disease. The model consists in the intracranial inoculation of the SLEV strain BeH 355964, a strain isolated from a symptomatic human patient in Brazil, in adult immunocompetent mice.



Inoculated mice presented SLEV replication in the brain, accompanied by tissue damage, disease signs, and mortality approximately 7 days post infection. Infection was characterized by the production of proinflammatory cytokines and interferons and by leukocyte recruitment to the brain, composed mainly by neutrophils and lymphocytes. In vitro experiments indicated that SLEV is able to replicate in both neurons and glia and caused neuronal death and cytokine production, respectively.



Altogether, intracranial SLEV infection leads to meningoencephalitis in mice, recapitulating several aspects of St. Louis encephalitis in humans. Our study indicates that the central nervous system (CNS) inflammation is a major component of SLEV-induced disease. This model may be useful to identify mechanisms of disease pathogenesis or resistance to SLEV infection.
Immunopharmacology, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. rafael.marques@lnbio.cnpem.br.|Present address: Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, São Paulo, Brazil. rafael.marques@lnbio.cnpem.br.
Rafael Elias
0000-0002-6949-0947
RE
Marques
Immunopharmacology, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Juliana L
JL
Del Sarto
Immunopharmacology, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Rebeca P F
RP
Rocha
Laboratório de Investigação em Neurodegeneração e Infecção, Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, Pará, Brazil.
Giovanni F
GF
Gomes
Laboratório de Imunorregulação de Doenças Infecciosas, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Allysson
A
Cramer
Laboratório de Apoptose, Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Milene A
MA
Rachid
Laboratório de Interação Microrganismo-Hospedeiro, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Danielle G
DG
Souza
Laboratório de Pesquisas em Virologia, Departamento de Doenças dermatológicas, Infecciosas e Parasitárias, Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, São Paulo, Brazil.
Maurício L
ML
Nogueira
Immunopharmacology, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Mauro M
MM
Teixeira
D000704:Analysis of Variance; D000818:Animals; D002461:Cell Line, Transformed; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004665:Encephalitis Virus, St. Louis / Q000502:physiology*; D004674:Encephalitis, St. Louis / Q000473:pathology* / Q000821:virology; D047209:Eosinophil Peroxidase / Q000378:metabolism; D006596:Hexosaminidases / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D013997:Time Factors; D019562:Viral Load
D016207:Cytokines; D047209:Eosinophil Peroxidase; D009195:Peroxidase; D006596:Hexosaminidases
Inflammation; Mouse model; SLEV; St. Louis encephalitis; Viral encephalitis