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Pathogens
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Neuropathogenesis of Arboviruses
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Neuropathogenesis of Arboviruses

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

Deadline for manuscript submissions: closed (15 December 2024) | Viewed by 9522

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,

Arboviruses (arthropod-borne viruses), which are transmitted through the bite of blood-feeding arthropods like mosquitoes, ticks, and sandflies, can trigger neurological disorders. These include encephalitis, paralysis, ophthalmological impairments, developmental defects, or neurological sequelae. Neurological disease caused by arboviral infections often affects young, elderly, and immunocompromised individuals and is becoming a growing public health issue globally. However, the neuropathogenesis of arboviruses is still largely unknown. 

The Special Issue aims to present the latest research on all aspects of the neuropathogenesis of arboviruses. Developing a better understanding of virus–host interactions in the nervous system will be crucial for the development of new therapeutics. Manuscripts of all types are welcome, including reviews, research articles, and short communications. We look forward to your valuable contributions.

Prof. Dr. Tian 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 2200 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

  • vector-borne viruses
  • encephalitis
  • arboviruses
  • neuropathogenesis
  • neuroinvasive
  • neurovirulence
  • blood–brain barrier
  • neuroinflammation
  • flavivirus
  • alphavirus

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Published Papers (4 papers)

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Research

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15 pages, 1959 KiB  
Article
VEEV TC-83 Triggers Dysregulation of the Tryptophan–Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice
by Chanida Fongsaran, Kelly T. Dineley, Slobodan Paessler and Irma E. Cisneros
Pathogens 2024, 13(5), 397; https://doi.org/10.3390/pathogens13050397 - 9 May 2024
Cited by 1 | Viewed by 1886
Abstract
Neurodegenerative diseases are chronic conditions affecting the central nervous system (CNS). Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid beta in the limbic and cortical brain regions. AD is presumed to result from genetic abnormalities or environmental factors, [...] Read more.
Neurodegenerative diseases are chronic conditions affecting the central nervous system (CNS). Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid beta in the limbic and cortical brain regions. AD is presumed to result from genetic abnormalities or environmental factors, including viral infections, which may have deleterious, long-term effects. In this study, we demonstrate that the Venezuelan equine encephalitis virus (VEEV) commonly induces neurodegeneration and long-term neurological or cognitive sequelae. Notably, the effects of VEEV infection can persistently influence gene expression in the mouse brain, suggesting a potential link between the observed neurodegenerative outcomes and long-term alterations in gene expression. Additionally, we show that alphavirus encephalitis exacerbates the neuropathological profile of AD through crosstalk between inflammatory and kynurenine pathways, generating a range of metabolites with potent effects. Using a mouse model for β-amyloidosis, Tg2576 mice, we found that cognitive deficits and brain pathology were more severe in Tg2576 mice infected with VEEV TC-83 compared to mock-infected controls. Thus, during immune activation, the kynurenine pathway plays a more active role in the VEEV TC-83-infected cells, leading to increases in the abundance of transcripts related to the kynurenine pathway of tryptophan metabolism. This pathway generates several metabolites with potent effects on neurotransmitter systems as well as on inflammation, as observed in VEEV TC-83-infected animals. Full article
(This article belongs to the Special Issue Neuropathogenesis of Arboviruses)
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Review

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32 pages, 2054 KiB  
Review
Neuropathogenesis of Encephalitic Alphaviruses in Non-Human Primate and Mouse Models of Infection
by Caitlin M. Woodson, Shannon K. Carney and Kylene Kehn-Hall
Pathogens 2025, 14(2), 193; https://doi.org/10.3390/pathogens14020193 - 14 Feb 2025
Viewed by 1222
Abstract
Encephalitic alphaviruses, including eastern, Venezuelan, and western equine encephalitis virus (EEEV, VEEV, and WEEV, respectively) are New World alphaviruses primarily transmitted by mosquitos that cause debilitating and lethal central nervous system (CNS) disease in both humans and horses. Despite over one hundred years [...] Read more.
Encephalitic alphaviruses, including eastern, Venezuelan, and western equine encephalitis virus (EEEV, VEEV, and WEEV, respectively) are New World alphaviruses primarily transmitted by mosquitos that cause debilitating and lethal central nervous system (CNS) disease in both humans and horses. Despite over one hundred years of research on these viruses, the underpinnings of the molecular mechanisms driving virally induced damage to the CNS remain unresolved. Moreover, virally induced encephalitis following exposure to these viruses causes catastrophic damage to the CNS, and survivors of infection often suffer from permanent neurological sequelae as a result of sustained neuroinflammation and neurological insults encountered. Animal models are undoubtedly invaluable tools in biomedical research, where physiologically relevant models are required to study pathogenesis and host–pathogen interactions. Here, we review the literature to examine nonhuman primate (NHP) and mouse models of infection for EEEV, VEEV, and WEEV. We provide a brief overview of relevant background information for each virus, including geography, epidemiology, and clinical disease. The primary focus of this review is to describe neuropathological features associated with CNS disease in NHP and mouse models of infection and compare CNS invasion and neuropathogenesis for aerosol, intranasal, and subcutaneous routes of exposure to EEEV, VEEV, and WEEV. Full article
(This article belongs to the Special Issue Neuropathogenesis of Arboviruses)
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19 pages, 359 KiB  
Review
Flaviviruses—Induced Neurological Sequelae
by Samantha Gabrielle Cody, Awadalkareem Adam, Andrei Siniavin, Sam S. Kang and Tian Wang
Pathogens 2025, 14(1), 22; https://doi.org/10.3390/pathogens14010022 - 31 Dec 2024
Viewed by 1212
Abstract
Flaviviruses, a group of single-stranded RNA viruses spread by mosquitoes or ticks, include several significant neurotropic viruses, such as West Nile virus (WNV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and Zika virus (ZIKV). These viruses can cause a range of neurological [...] Read more.
Flaviviruses, a group of single-stranded RNA viruses spread by mosquitoes or ticks, include several significant neurotropic viruses, such as West Nile virus (WNV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and Zika virus (ZIKV). These viruses can cause a range of neurological diseases during acute infection, from mild, flu-like symptoms to severe and fatal encephalitis. A total of 20–50% of patients who recovered from acute flavivirus infections experienced long-term cognitive issues. Here, we discuss these major neurotropic flaviviruses-induced clinical diseases in humans and the recent findings in animal models and provide insights into the underlying disease mechanisms. Full article
(This article belongs to the Special Issue Neuropathogenesis of Arboviruses)
24 pages, 3727 KiB  
Review
Zika Virus Neuropathogenesis—Research and Understanding
by Anna D. Metzler and Hengli Tang
Pathogens 2024, 13(7), 555; https://doi.org/10.3390/pathogens13070555 - 2 Jul 2024
Cited by 2 | Viewed by 4260
Abstract
Zika virus (ZIKV), a mosquito-borne flavivirus, is prominently associated with microcephaly in babies born to infected mothers as well as Guillain-Barré Syndrome in adults. Each cell type infected by ZIKV—neuronal cells (radial glial cells, neuronal progenitor cells, astrocytes, microglia cells, and glioblastoma stem [...] Read more.
Zika virus (ZIKV), a mosquito-borne flavivirus, is prominently associated with microcephaly in babies born to infected mothers as well as Guillain-Barré Syndrome in adults. Each cell type infected by ZIKV—neuronal cells (radial glial cells, neuronal progenitor cells, astrocytes, microglia cells, and glioblastoma stem cells) and non-neuronal cells (primary fibroblasts, epidermal keratinocytes, dendritic cells, monocytes, macrophages, and Sertoli cells)—displays its own characteristic changes to their cell physiology and has various impacts on disease. Here, we provide an in-depth review of the ZIKV life cycle and its cellular targets, and discuss the current knowledge of how infections cause neuropathologies, as well as what approaches researchers are currently taking to further advance such knowledge. A key aspect of ZIKV neuropathogenesis is virus-induced neuronal apoptosis via numerous mechanisms including cell cycle dysregulation, mitochondrial fragmentation, ER stress, and the unfolded protein response. These, in turn, result in the activation of p53-mediated intrinsic cell death pathways. A full spectrum of infection models including stem cells and co-cultures, transwells to simulate blood–tissue barriers, brain-region-specific organoids, and animal models have been developed for ZIKV research. Full article
(This article belongs to the Special Issue Neuropathogenesis of Arboviruses)
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