Long-Term, West Nile Virus-Induced Neurological Changes: a comparison of patients and rodent models, 2020, Fulton et al

Dolphin · Jul 23, 2020

Free full text:
https://www.sciencedirect.com/science/article/pii/S2666354620300703

Brain, Behavior, & Immunity - Health
Available online 18 July 2020, 100105

Review
Long-Term, West Nile Virus-Induced Neurological Changes: a comparison of patients and rodent models

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Corey D.M.Fulton123
David W.C.Beasley1234
Dennis A.Bente123
Kelly T.Dineley356
1
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas
2
Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA
3
Institute for Human Infections & Immunity, University of Texas Medical Branch, Galveston, TX
4
Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX
5
Center for Addiction Research, University of Texas Medical Branch, Galveston, Texas
6
Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, Galveston, TX
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Received 22 April 2020, Revised 7 July 2020, Accepted 12 July 2020, Available online 18 July 2020.

https://doi.org/10.1016/j.bbih.2020.100105

Highlights

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In patients with and without diagnosed WNND, there are long-lasting neurological sequelae that can mimic neurodegenerative diseases

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Some rodent models of WNV reproduce some of these changes with mechanisms similar to neurodegenerative diseases

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There is significant overlap between WNV and ND pathogenesis and this has been understudied

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Further research needs to be done to determine translatability of animal models and to establish mechanisms in human patients
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Abstract
West Nile virus (WNV) is a mosquito-borne virus that can cause severe neurological disease in those infected. Those surviving infection often present with long-lasting neurological changes that can severely impede their lives. The most common reported symptoms are depression, memory loss, and motor dysfunction. These sequelae can persist for the rest of the patients’ lives. The pathogenesis behind these changes is still being determined. Here, we summarize current findings in human cases and rodent models, and discuss how these findings indicate that WNV induces a state in the brain similar neurodegenerative diseases. Rodent models have shown that infection leads to persistent virus and inflammation. Initial infection in the hippocampus leads to neuronal dysfunction, synapse elimination, and astrocytosis, all of which contribute to memory loss, mimicking findings in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). WNV infection acts on pathways, such as ubiquitin-signaled protein degradation, and induces the production of molecules, including IL-1β, IFN-γ, and α-synuclein, that are associated with neurodegenerative diseases. These findings indicate that WNV induces neurological damage through similar mechanisms as neurodegenerative diseases, and that pursuing research into the similarities will help advance our understanding of the pathogenesis of WNV-induced neurological sequelae.

Keywords
West Nile virus
inflammation
neuroinflammation
cognition
WNV
virus
behavioral model
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Dolphin · Jul 23, 2020

Fatigue is a commonly reported sequelae in WNF/WNND patients(149, 150). One reported mechanism is the persistently elevated levels of pro-inflammatory cytokines up to five years post-infection(149, 150). Some of the cytokines correlated with fatigue included IFN-γ, IL-2, and IL-6. Besides the roles these cytokines play in controlling acute WNV infection . (52,98,127), and in ND, they have been implicated in chronic fatigue syndrome (CFS). CFS has previously been associated with viral infections(149, 150), including Epstein-Barr virus and herpesvirus-6. Elevated levels of IFN-γ have been associated with CFS(149, 150), and higher levels of the cytokine in serum correlates with increased severity of disease(149, 150). Plasma IL-6 is elevated in patients with CFS(149, 150), and has also been associated with MDD(149, 150) and fibromyalgia(149, 150). These studies indicate a common pathway leading to similar symptoms in patients suffering from CFS and those reporting fatigue after WNV infection.
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Hutan · Jul 24, 2020

The prevalence of sequelae among survivors of WNV infection varies between studies, but it is generally between 30% and 60%(14, 15, 16, 17). Reported sequelae include a wide range of deficits such as paralysis, memory loss, depression, and fatigue(18). These may last for months or for the rest of the patient’s life. The mechanisms that underlie these sequelae are poorly understood, and this review aims to catalog recent findings, both clinical and experimental, as well as provide guidance to advance our understanding of WNV-induced neurological sequelae.
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