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We used unbiased metagenomic next-generation sequencing to diagnose a fatal case of meningoencephalitis caused by St. Louis encephalitis virus in a patient from California in September 2016. This case is associated with the recent 2015-2016 reemergence of this virus in the southwestern United States.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

St. Louis encephalitis virus (SLEV, Flavivirus, Flaviviridae) is an emerging mosquito-borne pathogen in South America, with human SLEV encephalitis cases reported in Argentina and Brazil. Genotype III strains of SLEV were isolated from Culex quinquefasciatus mosquitoes in Cordoba, Argentina in 2005, during the largest SLEV outbreak ever reported in South America. The present study tested the hypothesis that the recent, epidemic SLEV strain exhibits greater virulence in birds as compared with a non-epidemic genotype III strain isolated from mosquitoes in Santa Fe Province 27 years earlier. The observed differences in infection parameters between adult House sparrows (Passer domesticus) that were needle-inoculated with either the epidemic or historic SLEV strain were not statistically significant. However, only the House sparrows that were infected with the epidemic strain achieved infectious-level viremia titers sufficient to infect Cx. spp. mosquitoes vectors. Furthermore, the vertebrate reservoir competence index values indicated an approximately 3-fold increase in amplification potential of House sparrows infected with the epidemic strain when pre-existing flavivirus-reactive antibodies were present, suggesting the possibility that antibody-dependent enhancement may increase the risk of avian-amplified transmission of SLEV in South America.