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Viruses 2014, 6(7), 2796-2825; doi:10.3390/v6072796

Mechanism of West Nile Virus Neuroinvasion: A Critical Appraisal

1
School of Veterinary Science, University of Queensland, Gatton, QLD, 4343, Australia
2
Australian Infectious Diseases Research Centre, University of Queensland, St. Lucia, QLD, 4072, Australia
3
School of Chemistry and Molecular Bioscience, University of Queensland, St Lucia, QLD, 4072, Australia
*
Author to whom correspondence should be addressed.
Received: 28 April 2014 / Revised: 9 July 2014 / Accepted: 10 July 2014 / Published: 18 July 2014
(This article belongs to the Section Animal Viruses)
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Abstract

West Nile virus (WNV) is an important emerging neurotropic virus, responsible for increasingly severe encephalitis outbreaks in humans and horses worldwide. However, the mechanism by which the virus gains entry to the brain (neuroinvasion) remains poorly understood. Hypotheses of hematogenous and transneural entry have been proposed for WNV neuroinvasion, which revolve mainly around the concepts of blood-brain barrier (BBB) disruption and retrograde axonal transport, respectively. However, an over‑representation of in vitro studies without adequate in vivo validation continues to obscure our understanding of the mechanism(s). Furthermore, WNV infection in the current rodent models does not generate a similar viremia and character of CNS infection, as seen in the common target hosts, humans and horses. These differences ultimately question the applicability of rodent models for pathogenesis investigations. Finally, the role of several barriers against CNS insults, such as the blood-cerebrospinal fluid (CSF), the CSF-brain and the blood-spinal cord barriers, remain largely unexplored, highlighting the infancy of this field. In this review, a systematic and critical appraisal of the current evidence relevant to the possible mechanism(s) of WNV neuroinvasion is conducted. View Full-Text
Keywords: West Nile virus; pathogenesis; neuroinvasion; blood-brain barrier; blood-CSF barrier; CSF-brain barrier; blood-spinal cord barrier; retrograde axonal transport West Nile virus; pathogenesis; neuroinvasion; blood-brain barrier; blood-CSF barrier; CSF-brain barrier; blood-spinal cord barrier; retrograde axonal transport
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Suen, W.W.; Prow, N.A.; Hall, R.A.; Bielefeldt-Ohmann, H. Mechanism of West Nile Virus Neuroinvasion: A Critical Appraisal. Viruses 2014, 6, 2796-2825.

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