1887

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Volume 102, Issue 2

Development of Rift valley fever encephalitis in rats is mediated by early infection of olfactory epithelium and neuroinvasion across the cribriform plate Open Access

Abstract

The zoonotic emerging Rift Valley fever virus (RVFV) causes sporadic disease in livestock and humans throughout Africa and the Saudi Arabian peninsula. Infection of people with RVFV can occur through mosquito bite or mucosal exposure during butchering or milking of infected livestock. Disease typically presents as a self-limiting fever; however, in rare cases, hepatitis, encephalitis and ocular disease may occur. Recent studies have illuminated the neuropathogenic mechanisms of RVFV in a rat aerosol infection model. Neurological disease in rats is characterized by breakdown of the blood–brain barrier late in infection, infiltration of leukocytes to the central nervous system (CNS) and massive viral replication in the brain. However, the route of RVFV entry into the CNS after inhalational exposure remains unknown. Here, we visualized the entire nasal olfactory route from snout to brain after RVFV infection using RNA hybridization and immunofluorescence microscopy. We found widespread RVFV-infected cells within the olfactory epithelium, across the cribriform plate, and in the glomerular region of the olfactory bulb within 2 days of infection. These results indicate that the olfactory tract is a major route of infection of the brain after inhalational exposure. A better understanding of potential neuroinvasion pathways can support the design of more effective therapeutic regiments for the treatment of neurological disease caused by RVFV.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): aerosol , cribriform plate , encephalitis , olfactory bulb , pathogenesis and Rift Valley fever virus
Funding
This study was supported by the:
  • National Institute of Allergy and Infectious Diseases (Award T32 AI060525)
    • Principle Award Recipient: Cynthia M McMillen
  • National Institute of Neurological Disorders and Stroke (Award R21NS088326)
    • Principle Award Recipient: Amy L Hartman
  • National Institute of Neurological Disorders and Stroke (Award R01NS101100)
    • Principle Award Recipient: Amy L Hartman
© 2021 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2020-11-24
2024-04-20
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Development of Rift valley fever encephalitis in rats is mediated by early infection of olfactory epithelium and neuroinvasion across the cribriform plate
J. Gen. Virol. 102, 001522 (2021); https://doi.org/10.1099/jgv.0.001522
/content/journal/jgv/10.1099/jgv.0.001522
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