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Zika virus (ZIKV) is an emerging flavivirus typically causing a dengue-like febrile illness, but neurological complications, such as microcephaly in newborns, have potentially been linked to this viral infection. We established a panel of in vitro assays to allow the identification of ZIKV inhibitors and demonstrate that the viral polymerase inhibitor 7-deaza-2’-C-methyladenosine (7DMA) efficiently inhibits replication. Infection of AG129 (IFN-α/β and IFN-γ receptor knock-out) mice with ZIKV resulted in acute neutrophilic encephalitis with viral antigens accumulating in neurons of the brain and spinal cord. Additionally, high levels of viral RNA were detected in the spleen, liver and kidney, and levels of IFN-γ and IL-18 were systematically increased in serum of ZIKV-infected mice. Interestingly, the virus was also detected in testicles of infected mice. In line with its in vitro anti-ZIKV activity, 7DMA reduced viremia and delayed virus-induced morbidity and mortality in infected mice, which also validates this small animal model to assess the in vivo efficacy of novel ZIKV inhibitors. Since AG129 mice can generate an antibody response, and have been used in dengue vaccine studies, the model can also be used to assess the efficacy of ZIKV vaccines., Author Summary A robust cell-based antiviral assay was developed that allows to screen for and validate novel inhibitors of Zika virus (ZIKV) replication. The viral polymerase inhibitor 7-deaza-2’-C-methyladenosine (7DMA) was identified as a potent ZIKV inhibitor. A mouse model for ZIKV infections, which was validated for antiviral studies, demonstrated that 7DMA markedly delays virus-induced disease in this model.

St. Louis encephalitis virus (SLEV) is a causative agent of encephalitis in humans in the Western hemisphere. SLEV is a positive-sense RNA virus that belongs to the Flavivirus genus, which includes West Nile encephalitis virus, Japanese encephalitis virus, Dengue virus and other medically important viruses. Recently, we isolated a SLEV strain from the brain of a horse with neurological signs in the countryside of Minas Gerais, Brazil. The SLEV isolation was confirmed by reverse-transcription RT-PCR and sequencing of the E protein gene. Virus identity was also confirmed by indirect immunofluorescence using commercial antibodies against SLEV. To characterize this newly isolated strain in vivo, serial passages in newborn mice were performed and led to hemorrhagic manifestations associated with recruitment of inflammatory cells into the central nervous system of newborns. In summary this is the first isolation of SLEV from a horse with neurological signs in Brazil., Author Summary St. Louis encephalitis virus (SLEV), a member of the Flavivirus genus, which includes West Nile encephalitis virus, Japanese encephalitis virus, Dengue virus, and other medically important viruses, is a cause of encephalitis in humans and animals. SLEV is considered endemic in the Americas, and currently there is no vaccine or specific treatment available for controlling of preventing SLEV-induced encephalitis. In this study we describe the first isolation of SLEV from an adult male horse with neurologic disease, which was further characterized by molecular and serological methods. Phylogenetic analysis of a 903 base pairs amplified sequence from partial Envelope (E) gene region indicated that the isolate from the horse was within the cluster of the VB genotype. In addition, inoculation of the SLEV isolate intracranially in newborn mice resulted in circulatory and neurological changes. This is the first report of isolation of SLEV from a horse with neurological disease in Brazil.