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Viruses2014; 6(7); 2796-2825; doi: 10.3390/v6072796

Mechanism of West Nile virus neuroinvasion: a critical appraisal.

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.
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Publication Date: 2014-07-18 PubMed ID: 25046180PubMed Central: PMC4113794DOI: 10.3390/v6072796Google Scholar: Lookup
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  • Non-U.S. Gov't
  • Review

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article critically examines the current understanding of how the West Nile virus (WNV) invades the brain. The authors highlight the lack of in-vivo validation for existing hypotheses and question the applicability of rodent models for this pathogenesis, suggesting further research is necessary.

Overview of West Nile Virus and Neuroinvasion

  • The authors of this paper begin by discussing the West Nile virus (WNV), an emerging neurotropic virus responsible for severe encephalitis outbreaks in humans and horses across the globe. The main focus of the paper is the mechanism by which the virus invades the brain—a process referred to as “neuroinvasion.”
  • The authors point out the current lack of understanding of this mechanism and underline the need for further investigation.

Theories of Neuroinvasion: Hematogenous and Transneural Entry

  • The paper explores two hypotheses of how WNV might invade the brain—through hematogenous entry (bloodstream) and transneural entry (nervous system).
  • The hematogenous route suggests that WNV causes a disruption in the blood-brain barrier (BBB), allowing the virus to enter the brain. The transneural route, on the other hand, proposes that the virus uses retrograde axonal transport to reach the brain.

Limitations of Current Research

  • The authors criticise the over-reliance on in vitro (lab-grown) studies in current research, arguing that these lack sufficient in vivo (within a living organism) validation and hence may not reflect accurately the actual mechanism of neuroinvasion.
  • It is further highlighted that the infection symptoms in commonly used rodent models do not adequately represent the characteristics of the infection in the most common hosts – humans and horses. This discrepancy raises questions about the suitability of rodent models for exploring the pathogenesis of WNV.
  • Additionally, the authors highlight unexplored areas of research, including the role of barriers like the blood-cerebrospinal fluid (CSF), the CSF-brain, and the blood-spinal cord barriers against Central Nervous System (CNS) infections.

Conclusion and Implications

  • The paper concludes with a comprehensive appraisal of the current evidence regarding the potential mechanisms of WNV neuroinvasion. The authors underscore the gaps in current knowledge and emphasize the necessity for further research to fully understand the virus’s neuroinvasion.

Cite This Article

APA
Suen WW, Prow NA, Hall RA, Bielefeldt-Ohmann H. (2014). Mechanism of West Nile virus neuroinvasion: a critical appraisal. Viruses, 6(7), 2796-2825. https://doi.org/10.3390/v6072796

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 6
Issue: 7
Pages: 2796-2825

Researcher Affiliations

Suen, Willy W
  • School of Veterinary Science, University of Queensland, Gatton, QLD, 4343, Australia. w.suen@uq.edu.au.
Prow, Natalie A
  • Australian Infectious Diseases Research Centre, University of Queensland, St. Lucia, QLD, 4072, Australia. n.prow@uq.edu.au.
Hall, Roy A
  • Australian Infectious Diseases Research Centre, University of Queensland, St. Lucia, QLD, 4072, Australia. roy.hall@uq.edu.au.
Bielefeldt-Ohmann, Helle
  • School of Veterinary Science, University of Queensland, Gatton, QLD, 4343, Australia. h.bielefeldtohmann1@uq.edu.au.

MeSH Terms

  • Adherens Junctions / metabolism
  • Adherens Junctions / virology
  • Animals
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / virology
  • Blood-Nerve Barrier / metabolism
  • Blood-Nerve Barrier / virology
  • Brain / pathology
  • Brain / virology
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Encephalitis, Viral / physiopathology
  • Encephalitis, Viral / virology
  • Gene Expression Regulation, Viral
  • Horses
  • Humans
  • Spinal Cord / pathology
  • Spinal Cord / virology
  • Tight Junctions / metabolism
  • Tight Junctions / virology
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Viremia / physiopathology
  • Viremia / virology
  • Virus Internalization
  • West Nile virus / genetics
  • West Nile virus / metabolism
  • West Nile virus / pathogenicity

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