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Walters, Aaron W.; Kujawa, Michael R.; Albe, Joseph R.; Reed, Douglas S.; Klimstra, William B.; Hartman, Amy L.
Virology, 01/2019, Volume: 526, Issue: CJournal Article
Rift Valley fever virus (RVFV) is a zoonotic disease of livestock that causes several clinical outcomes in people including febrile disease, hemorrhagic fever, and/or encephalitis. After aerosol infection with RVFV, Lewis rats develop lethal encephalitic disease, and we use this as a model for studying disease mechanisms of RVFV infection in the brain. Permeability of the brain vasculature in relation to virus invasion and replication is not known. Here, we found that vascular permeability in the brain occurred late in the course of infection and corresponded temporally to expression of matrix metalloproteinase-9 (MMP-9). Virus replication was ongoing within the central nervous system for several days prior to detectable vascular leakage. Based on this study, vascular permeability was not required for entry of RVFV into the brain of rats. Prevention of vascular leakage late in infection may be an important component for prevention of lethal neurological disease in the rat model. •After inhalational infection of rats with RVFV, virus spreads from the olfactory bulb posteriorly through the brain.•Vascular permeability in the brain occurred late in the course of RVFV infection, after the virus was replicating in the brain.•Vascular leakage in the brain corresponded temporally to expression of matrix metalloproteinase-9 (MMP-9).•Prevention of vascular permeability late in infection may be important for protection from neurological disease in rats.
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