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Pathogens
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Current Research on Arboviral Encephalitis
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Current Research on Arboviral Encephalitis

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

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 13532

Special Issue Editors

Dr. Holly Hughes

E-Mail Website
Guest Editor
Arbovial Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA
Interests: whole-genome sequencing; viral evolution; immunology
Dr. Emily Davis

E-Mail Website
Guest Editor Assistant
Arbovial Diseases Branch, Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA
Interests: host–pathogen interaction; intra-host evolution; high-throughput sequencing

Special Issue Information

Dear Colleagues,

Arboviruses (arthropod-borne viruses) are transmitted to humans through the bite of blood-feeding arthropods, such as mosquitoes, ticks, and sandflies. Neurological disease is an increasingly important clinical presentation of arboviral infections, often affecting young, elderly, and immunocompromised individuals. Arboviruses capable of causing encephalitis are found throughout the world. While some viruses have widespread distribution such as West Nile virus, many are focally distributed, such as Eyach virus. Of special note, encephalitic arboviruses belong to several different viral families including Flaviviridae, Togaviridae, Peribunyaviridae, Phenuiviridae, and Reoviridae. These families include viruses utilizing RNA genomes with several different coding strategies including positive sense, negative sense, ambisense, segmented, or double-stranded RNA. This breadth of diversity presents unique challenges to surveillance, diagnosis, treatment, and control. 

This Special Issue will provide a broad overview of the (re)emergence, epidemiology, control, pathogenesis, and diagnosis of the wide breadth of arboviruses causing encephalitis. Original research articles (including short reports) or review articles covering topics including, but not limited to, diagnostic tools, vector surveillance and control, virus evolution, epidemiology or clinical findings, virus–host interactions, antivirals, therapeutics, or vaccine development are suitable and highly valuable contributions. Readers will benefit from the current state of research for commonly known viruses, as well as rare and orphan pathogens.

Dr. Holly Hughes
Guest Editor

Dr. Emily Davis
Guest Editor Assistant

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

  • arbovirus
  • encephalitis
  • diagnostics
  • phylogenetics
  • surveillance
  • vector control
  • therapeutics

Published Papers (6 papers)

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Research

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20 pages, 8980 KiB  
Article
Powassan Virus Induces Structural Changes in Human Neuronal Cells In Vitro and Murine Neurons In Vivo
by Jacob Nelson, Lorenzo Ochoa, Paula Villareal, Tiffany Dunn, Ping Wu, Gracie Vargas and Alexander N. Freiberg
Pathogens 2022, 11(10), 1218; https://doi.org/10.3390/pathogens11101218 - 21 Oct 2022
Cited by 3 | Viewed by 2680
Abstract
Powassan virus (POWV) is a tick-borne flavivirus (TBFV) that can cause severe encephalitis in humans with a case–fatality rate as high as 11%. Patients who survive severe encephalitic disease can develop long-term neurological sequelae that can be debilitating and life-long. In this study, [...] Read more.
Powassan virus (POWV) is a tick-borne flavivirus (TBFV) that can cause severe encephalitis in humans with a case–fatality rate as high as 11%. Patients who survive severe encephalitic disease can develop long-term neurological sequelae that can be debilitating and life-long. In this study, we have sought to characterize a primary human fetal brain neural stem cell system (hNSC), which can be differentiated into neuron and astrocyte co-cultures, to serve as a translational in vitro system for infection with POWV and a comparative mosquito-borne flavivirus (MBFV), West Nile virus (WNV). We found that both viruses are able to infect both cell types in the co-culture and that WNV elicits a strong inflammatory response characterized by increased cytokines IL-4, IL-6, IL-8, TNF-α and IL-1β and activation of apoptosis pathways. POWV infection resulted in fewer cytokine responses, as well as less detectable apoptosis, while neurons infected with POWV exhibited structural aberrations forming in the dendrites. These anomalies are consistent with previous findings in which tick-borne encephalitis virus (TBEV) infected murine primary neurons formed laminal membrane structures (LMS). Furthermore, these structural aberrations are also recapitulated in brain tissue from infected mice. Our findings indicate that POWV is capable of infecting human primary neurons and astrocytes without causing apparent widespread apoptosis, while forming punctate structures reminiscent with LMS in primary human neurons and in vivo. Full article
(This article belongs to the Special Issue Current Research on Arboviral Encephalitis)
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9 pages, 2994 KiB  
Communication
Molecular Characterization of HN1304M, a Cat Que Virus Isolated from Midges in China
by Ziqian Xu, Lei Cao, Liang Cai, Shihong Fu, Kai Nie, Qikai Yin, Yuxi Cao, Guoping Liu, Yunzhi Liu, Hong Zhang, Lidong Gao, Ying He, Huanyu Wang and Guodong Liang
Pathogens 2022, 11(9), 1049; https://doi.org/10.3390/pathogens11091049 - 15 Sep 2022
Cited by 2 | Viewed by 1444
Abstract
The Cat Que orthobunyavirus has been found in mosquitoes, birds, pigs, and humans, suggesting its wide range of hosts and potential public health implications. During arbovirus surveillance in 2013, the HN1304M virus was isolated from naturally occurring Culicoides biting midges in Hunan Province, [...] Read more.
The Cat Que orthobunyavirus has been found in mosquitoes, birds, pigs, and humans, suggesting its wide range of hosts and potential public health implications. During arbovirus surveillance in 2013, the HN1304M virus was isolated from naturally occurring Culicoides biting midges in Hunan Province, southern China. The virus was cytopathic to BHK-21 cells and showed stable passage, but was not cytopathic to C6/36 cells. Determination and analysis of the viral genome sequence revealed that HN1304M is an RNA virus with three gene segments, namely, L, M, and S. The nucleotide and amino acid sequence homologies of HN1304M to Cat Que viruses in the Manzanilla species complex were 90.3–99.4%, and 95–100%, respectively, while the homologies to other viruses in this species complex were 74–86.6% and 78.1–96.1%, respectively. A phylogenetic analysis of the viral genes revealed that HN1304M formed an evolutionary branch with other Cat Que viruses isolated from mosquitoes, pigs, birds, and humans, which was completely independent of the other viruses in this complex. The fact that the Cat Que virus was isolated from Culicoides suggests that biting midges may participate in the natural circulation of Cat Que viruses. Full article
(This article belongs to the Special Issue Current Research on Arboviral Encephalitis)
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10 pages, 566 KiB  
Article
A Preliminary Study of Proinflammatory Cytokines and Depression Following West Nile Virus Infection
by Allison Lino, Timothy A. Erickson, Melissa S. Nolan, Kristy O. Murray and Shannon E. Ronca
Pathogens 2022, 11(6), 650; https://doi.org/10.3390/pathogens11060650 - 4 Jun 2022
Cited by 3 | Viewed by 2119
Abstract
West Nile virus (WNV) is a neurotropic flavivirus that can cause acute febrile illness leading to neuroinvasive disease. Depression is a well-described outcome following infection, but the underlying pathogenic mechanisms are unknown. Proinflammatory cytokines play important roles in WNV infection, but their role [...] Read more.
West Nile virus (WNV) is a neurotropic flavivirus that can cause acute febrile illness leading to neuroinvasive disease. Depression is a well-described outcome following infection, but the underlying pathogenic mechanisms are unknown. Proinflammatory cytokines play important roles in WNV infection, but their role in depression post-WNV remains unstudied. This research aimed to retrospectively evaluate associations between proinflammatory cytokines and new onset depression in a WNV cohort. Participants with asymptomatic WNV infection were significantly less likely to report new onset depression when compared to those with symptomatic disease. Participants with encephalitis and obesity were significantly more likely to report new onset depression post-infection. Based on univariate analysis of 15 antiviral or proinflammatory cytokines, depression was associated with elevated MCP-1 and decreased TNFα, whereas G-CSF was significantly elevated in those with a history of neuroinvasive WNV. However, no cytokines were statistically significant after adjusting for multiple comparisons using the Bonferroni method. While symptomatic WNV infection, encephalitis, and obesity were associated with new onset depression following infection, the role of proinflammatory cytokines requires additional studies. Further research involving paired acute-convalescent samples, larger sample sizes, and additional data points would provide additional insight into the impact of the inflammatory response on WNV-mediated depression. Full article
(This article belongs to the Special Issue Current Research on Arboviral Encephalitis)
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13 pages, 19097 KiB  
Article
Two Rhabdoviruses, One Novel, Isolated from Armigeres subalbatus in China
by Xiuyan Xu, Jing Wang, Hong Liu, Qinyan Wang, Shihong Fu, Jun Zhang, Bin Wang, Ying He, Fan Li, Kai Nie, Songtao Xu, Huanyu Wang, Xiaoqing Lu, Mang Shi and Guodong Liang
Pathogens 2022, 11(6), 624; https://doi.org/10.3390/pathogens11060624 - 27 May 2022
Cited by 2 | Viewed by 1668
Abstract
The family Rhabdoviridae contain important human and mammalian pathogens that are vectored by different arthropod species. The ground supernatants of mosquitoes were used to inoculate in BHK-21 and C6/36 cells for virus isolation. Then, the viral complete genome sequence was obtained and used [...] Read more.
The family Rhabdoviridae contain important human and mammalian pathogens that are vectored by different arthropod species. The ground supernatants of mosquitoes were used to inoculate in BHK-21 and C6/36 cells for virus isolation. Then, the viral complete genome sequence was obtained and used for phylogenetic analysis. In this study, we observed a cytopathic effect (CPE) in mosquito cells (C6/36) and rod-like virion after inoculating a pool of Armigeres subalbatus samples collected in Shanxi Province, China, in 2019 (SX1916). Meta-transcriptomics sequencing revealed the presence of two distinctive rhabdoviruses with similar abundance levels, namely, Shanxi Armigeres subalbatus rhabdovirus (SXARV) and Shanxi Arboretum virus (SXABTV). Despite the fact that the SXARV genome (9590 nt) was much shorter than that of SXABTV (11,480 nt), both belonged to the Almendravirus group within Rhabdoviridae whose genomes encoded five proteins (N, P, M, G, and L) and a small hydrophobin (U1) and the difference in lengths is mainly caused by a substantially shorter N protein encoded by SXARV. On the phylogenetic tree, SXABTV was closely related (90.7% amino acid identity at L protein) with the Arboretum virus isolated from Psorophora albigenu mosquitoes in Peru in 2014, whereas SXARV was distantly related to Rio Chico virus (63.3% amino acid identity), a genetic distance large enough to be defined as a new species within Rhabdoviridae. Collectively, we report a simultaneous isolation of two related rhabdoviruses from Armigeres subalbatus that marked the circulation of almendraviruses in Shanxi, China. Full article
(This article belongs to the Special Issue Current Research on Arboviral Encephalitis)
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8 pages, 531 KiB  
Article
Laboratory Validation of a Real-Time RT-PCR Assay for the Detection of Jamestown Canyon Virus
by Holly R. Hughes, Joan L. Kenney, Brandy J. Russell and Amy J. Lambert
Pathogens 2022, 11(5), 536; https://doi.org/10.3390/pathogens11050536 - 3 May 2022
Cited by 1 | Viewed by 1821
Abstract
The neuroinvasive disease caused by Jamestown Canyon virus (JCV) infection is rare. However, increasing incidence and widespread occurrence of the infection make JCV a growing public health concern. Presently, clinical diagnosis is achieved through serological testing, and mosquito pool surveillance requires virus isolation [...] Read more.
The neuroinvasive disease caused by Jamestown Canyon virus (JCV) infection is rare. However, increasing incidence and widespread occurrence of the infection make JCV a growing public health concern. Presently, clinical diagnosis is achieved through serological testing, and mosquito pool surveillance requires virus isolation and identification. A rapid molecular detection test, such as real-time RT-PCR, for diagnosis and surveillance of JCV has not been widely utilized. To enhance testing and surveillance, here, we describe the development and validation of a real-time RT-PCR test for the detection of JCV RNA. Three primer and probe sets were evaluated for analytical sensitivity and specificity. One probe set, JCV132FAM, was found to be the most sensitive test detecting 7.2 genomic equivalents/µL. While less sensitive, a second probe set JCV231cFAM was the most specific test with limited detection of Keystone virus at high RNA loads. Taken together, these data indicate both probe sets can be utilized for a primary sensitive screening assay and a secondary specific confirmatory assay. While both primer and probe sets detected high viral loads of Keystone virus, these assays did not detect any virus in the California encephalitis virus clade, including negative detection of the medically important La Crosse virus (LACV) and snowshoe hare virus (SSHV). The real-time RT-PCR assay described herein could be utilized in diagnosis and surveillance in regions with co-circulation of JCV and LACV or SSHV to inform public health action. Full article
(This article belongs to the Special Issue Current Research on Arboviral Encephalitis)
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Review

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13 pages, 1753 KiB  
Review
Getah Virus (Alphavirus): An Emerging, Spreading Zoonotic Virus
by Bin Li, Huanyu Wang and Guodong Liang
Pathogens 2022, 11(8), 945; https://doi.org/10.3390/pathogens11080945 - 20 Aug 2022
Cited by 9 | Viewed by 3036
Abstract
Getah virus (GETV) is a zoonotic virus transmitted by mosquitoes, belonging to the Togaviridae family, Alphavirus genus. It was first isolated from mosquitoes in Malaysia in 1955, being widespread in island countries in the South Pacific region. Since the beginning of the 21st [...] Read more.
Getah virus (GETV) is a zoonotic virus transmitted by mosquitoes, belonging to the Togaviridae family, Alphavirus genus. It was first isolated from mosquitoes in Malaysia in 1955, being widespread in island countries in the South Pacific region. Since the beginning of the 21st century, GETV expanded its range and geographical distribution from low-latitude tropical regions to 60° north latitude, being isolated from 17 different species of mosquitoes belonging to five genera of Culicidae (Culex, Anopheles, Armigeres, Aedes and Mansonia), as well as from midges in Eurasia. Molecular genetic evolution analysis revealed large molecular differences between the mosquitoes currently circulating Eurasia and those in the South Pacific in 1950s. The number of disease outbreaks caused by GETV in animals is increasing alongside the types of animals infected, from horses and pigs to cattle, blue foxes and red pandas. The disease burden is severely underestimated, and the economic cost to livestock production remains unknown. Herein, we review GETV temporal and spatial distribution, molecular genetic evolution, transmission and data on disease outbreaks. This work provides a reference for public health workers engaged in GETV research and zoonotic disease prevention and control. Full article
(This article belongs to the Special Issue Current Research on Arboviral Encephalitis)
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