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Pathogens
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Pathogenesis of West Nile Virus
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Pathogenesis of West Nile Virus

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (20 March 2020) | Viewed by 31539

Special Issue Editor

Prof. Dr. Tian Wang

E-Mail Website
Guest Editor
Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA
Interests: emerging and re-emerging RNA viruses; host immunity; neuropathogenesis; vaccine development; antiviral agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

West Nile virus (WNV) is a member of the genus of Flavivirus, a group of plus-sense, single-stranded RNA viruses. It has been the leading cause of viral encephalitis in the United States for nearly two decades. The WNV genome is about 11,000 nucleotides in length, which is translated and processed into ten proteins—three structural proteins (envelope (E), membrane, and nucleocapsid) and seven nonstructural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5).  Human infection results from mosquito bite, blood transfusion, organ transplantation, breast feeding, and in utero or occupational exposure. The features of acute illness in humans range from WN fever to neuroinvasive conditions, including meningitis, encephalitis, acute flaccid paralysis, and death. In addition, up to 50% of WNV convalescent patients have been reported to have long-term neurological sequelae or chronic kidney disease, which occur 6 to 12 months after the acute infection. Currently, there is no specific therapeutic agent for treatment of WNV infection, and an approved vaccine is not available for humans.

In this Special Issue, we would like to invite submission of original research or review manuscripts that cover virology, immunology, clinical studies, animal models, and transmission aspects of WNV infection. We hope the manuscripts from this Special Issue will provide new insights into WNV pathogenesis. I look forward to your contribution!

Prof. Tian (Tina) Wang
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pathogens is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • West Nile virus
  • pathogenesis
  • host immunity
  • animal models

Published Papers (4 papers)

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Research

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34 pages, 4778 KiB  
Article
An Acute Stress Model in New Zealand White Rabbits Exhibits Altered Immune Response to Infection with West Nile Virus
by Willy W. Suen, Mitchell Imoda, Albert W. Thomas, Nur N.B.M. Nasir, Nawaporn Tearnsing, Wenqi Wang and Helle Bielefeldt-Ohmann
Pathogens 2019, 8(4), 195; https://doi.org/10.3390/pathogens8040195 - 18 Oct 2019
Cited by 4 | Viewed by 2978
Abstract
The immune competence of an individual is a major determinant of morbidity in West Nile virus (WNV)-infection. Previously, we showed that immunocompetent New Zealand White rabbits (NZWRs; Oryctolagus cuniculus) are phenotypically resistant to WNV-induced disease, thus presenting a suitable model for study [...] Read more.
The immune competence of an individual is a major determinant of morbidity in West Nile virus (WNV)-infection. Previously, we showed that immunocompetent New Zealand White rabbits (NZWRs; Oryctolagus cuniculus) are phenotypically resistant to WNV-induced disease, thus presenting a suitable model for study of virus-control mechanisms. The current study used corticosteroid-treated NZWRs to model acute “stress”-related immunosuppression. Maximal effects on immune parameters were observed on day 3 post dexamethasone-treatment (pdt). However, contrary to our hypothesis, intradermal WNV challenge at this time pdt produced significantly lower viremia 1 day post-infection (dpi) compared to untreated controls, suggestive of changes to antiviral control mechanisms. To examine this further, RNAseq was performed on RNA extracted from draining lymph node—the first site of virus replication and immune detection. Unaffected by dexamethasone-treatment, an early antiviral response, primarily via interferon (IFN)-I, and induction of a range of known and novel IFN-stimulated genes, was observed. However, treatment was associated with expression of a different repertoire of IFN-α-21-like and IFN-ω-1-like subtypes on 1 dpi, which may have driven the different chemokine response on 3 dpi. Ongoing expression of Toll-like receptor-3 and transmembrane protein-173/STING likely contributed to signaling of the treatment-independent IFN-I response. Two novel genes (putative HERC6 and IFIT1B genes), and the SLC16A5 gene were also highlighted as important component of the transcriptomic response. Therefore, the current study shows that rabbits are capable of restricting WNV replication and dissemination by known and novel robust antiviral mechanisms despite environmental challenges such as stress. Full article
(This article belongs to the Special Issue Pathogenesis of West Nile Virus)
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Review

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23 pages, 1111 KiB  
Review
Comparative Pathology of West Nile Virus in Humans and Non-Human Animals
by Alex D. Byas and Gregory D. Ebel
Pathogens 2020, 9(1), 48; https://doi.org/10.3390/pathogens9010048 - 07 Jan 2020
Cited by 39 | Viewed by 11859
Abstract
West Nile virus (WNV) continues to be a major cause of human arboviral neuroinvasive disease. Susceptible non-human vertebrates are particularly diverse, ranging from commonly affected birds and horses to less commonly affected species such as alligators. This review summarizes the pathology caused by [...] Read more.
West Nile virus (WNV) continues to be a major cause of human arboviral neuroinvasive disease. Susceptible non-human vertebrates are particularly diverse, ranging from commonly affected birds and horses to less commonly affected species such as alligators. This review summarizes the pathology caused by West Nile virus during natural infections of humans and non-human animals. While the most well-known findings in human infection involve the central nervous system, WNV can also cause significant lesions in the heart, kidneys and eyes. Time has also revealed chronic neurologic sequelae related to prior human WNV infection. Similarly, neurologic disease is a prominent manifestation of WNV infection in most non-human non-host animals. However, in some avian species, which serve as the vertebrate host for WNV maintenance in nature, severe systemic disease can occur, with neurologic, cardiac, intestinal and renal injury leading to death. The pathology seen in experimental animal models of West Nile virus infection and knowledge gains on viral pathogenesis derived from these animal models are also briefly discussed. A gap in the current literature exists regarding the relationship between the neurotropic nature of WNV in vertebrates, virus propagation and transmission in nature. This and other knowledge gaps, and future directions for research into WNV pathology, are addressed. Full article
(This article belongs to the Special Issue Pathogenesis of West Nile Virus)
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9 pages, 1357 KiB  
Review
West Nile Virus Induced Cell Death in the Central Nervous System
by Bi-Hung Peng and Tian Wang
Pathogens 2019, 8(4), 215; https://doi.org/10.3390/pathogens8040215 - 01 Nov 2019
Cited by 23 | Viewed by 3894
Abstract
West Nile virus (WNV), a mosquito-borne, single-stranded flavivirus, has caused annual outbreaks of viral encephalitis in the United States since 1999. The virus induces acute infection with a clinical spectrum ranging from a mild flu-like febrile symptom to more severe neuroinvasive conditions, including [...] Read more.
West Nile virus (WNV), a mosquito-borne, single-stranded flavivirus, has caused annual outbreaks of viral encephalitis in the United States since 1999. The virus induces acute infection with a clinical spectrum ranging from a mild flu-like febrile symptom to more severe neuroinvasive conditions, including meningitis, encephalitis, acute flaccid paralysis, and death. Some WNV convalescent patients also developed long-term neurological sequelae. Neither the treatment of WNV infection nor an approved vaccine is currently available for humans. Neuronal death in the central nervous system (CNS) is a hallmark of WNV-induced meningitis and encephalitis. However, the underlying mechanisms of WNV-induced neuronal damage are not well understood. In this review, we discuss current findings from studies of WNV infection in vitro in the CNS resident cells and the in vivo animal models, and provide insights into WNV-induced neuropathogenesis. Full article
(This article belongs to the Special Issue Pathogenesis of West Nile Virus)
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21 pages, 861 KiB  
Review
Current Understanding of West Nile Virus Clinical Manifestations, Immune Responses, Neuroinvasion, and Immunotherapeutic Implications
by Fengwei Bai, E. Ashley Thompson, Parminder J. S. Vig and A. Arturo Leis
Pathogens 2019, 8(4), 193; https://doi.org/10.3390/pathogens8040193 - 16 Oct 2019
Cited by 57 | Viewed by 11483
Abstract
West Nile virus (WNV) is the most common mosquito-borne virus in North America. WNV-associated neuroinvasive disease affects all ages, although elderly and immunocompromised individuals are particularly at risk. WNV neuroinvasive disease has killed over 2300 Americans since WNV entered into the United States [...] Read more.
West Nile virus (WNV) is the most common mosquito-borne virus in North America. WNV-associated neuroinvasive disease affects all ages, although elderly and immunocompromised individuals are particularly at risk. WNV neuroinvasive disease has killed over 2300 Americans since WNV entered into the United States in the New York City outbreak of 1999. Despite 20 years of intensive laboratory and clinical research, there are still no approved vaccines or antivirals available for human use. However, rapid progress has been made in both understanding the pathogenesis of WNV and treatment in clinical practices. This review summarizes our current understanding of WNV infection in terms of human clinical manifestations, host immune responses, neuroinvasion, and therapeutic interventions. Full article
(This article belongs to the Special Issue Pathogenesis of West Nile Virus)
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