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Biomedicines
Special Issues
Encephalitis and Viral Infection: Mechanisms and Therapies
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Encephalitis and Viral Infection: Mechanisms and Therapies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Neurobiology and Clinical Neuroscience".

Deadline for manuscript submissions: 30 November 2024 | Viewed by 2530

Special Issue Editors

Dr. Bradley S. Hollidge

E-Mail Website
Guest Editor
REGENXBIO Inc., Rockville, MD, USA
Interests: neurovirology; gene therapy; neuroinflammation; arboviruses
Dr. Samantha S. Soldan

E-Mail Website
Guest Editor
Wistar Institute, Philadelphia, PA, USA
Interests: T lymphocytes; microbiology; pathogenesis; virology; B lymphocytes; human herpesvirus 4; EBV-encoded nuclear antigen 1; epstein–barr virus and multiple sclerosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue offers a platform for researchers to delve into the intricate relationship between neurovirology, encephalitis, and efficient therapies. Neurovirology and encephalitis are complex and often intertwined fields that are informative to the gene therapy field for treating neurologic diseases. In addition, recent advancements in gene therapies have opened new avenues for understanding and treating these encephalitic and neurologic diseases. This Special Issue acts as a bridge, fostering interdisciplinary collaboration and advancing medical knowledge.

We invite original research articles and reviews that contribute to the understanding of the following aspects within the scope of this Special Issue:

Neurovirology: Investigations into the molecular mechanisms underlying neurotropic viral infections, their impact on neural function, and the development of antiviral strategies.

Encephalitis: Studies on the etiology, pathogenesis, diagnosis, and management of encephalitis, with a focus on both infectious and autoimmune forms.

Gene therapy: Research on the development and application of gene therapies for neurologic diseases, including the use of viral vectors, gene editing techniques, and immunomodulatory approaches.

Interdisciplinary approaches: Contributions that bridge the gap between neurovirology, encephalitis, and gene therapies, offering novel insights, therapeutic strategies, and potential translational applications.

By bringing together experts from these diverse fields, this Special Issue seeks to foster collaboration, stimulate innovative research, and ultimately contribute to the development of novel therapeutic interventions for neuroviral infections, encephalitis, and neurologic diseases. We welcome manuscripts that explore the intersections of these disciplines, providing a holistic view of the challenges and opportunities in this critical area of biomedical science.

Dr. Bradley S. Hollidge
Dr. Samantha S. Soldan
Guest Editors

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. Biomedicines 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 2600 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

  • neurovirology
  • encephalitis
  • gene therapy
  • viral vectors
  • virology
  • immunology
  • neuroscience
  • gene editing

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Published Papers (2 papers)

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Research

16 pages, 1887 KiB  
Article
Post-Herpetic Anti-NMDAR Encephalitis in Denmark: Current Status and Future Challenges
by Anna Søgaard, Charlotte Aaberg Poulsen, Nadia Zeeberg Belhouche, Alberte Thybo, Siv Tonje Faret Hovet, Lykke Larsen, Christine Nilsson, Morten Blaabjerg and Mette Scheller Nissen
Biomedicines 2024, 12(9), 1953; https://doi.org/10.3390/biomedicines12091953 - 27 Aug 2024
Viewed by 694
Abstract
It is well known that N-methyl-D-aspartate receptor encephalitis (NMDARE) can be triggered by infectious encephalitis such as herpes simplex virus 1 encephalitis (HSE). However, the incidence of post-HSE NMDARE in Denmark is unknown. We reviewed literature cases and compared these to retrospectively [...] Read more.
It is well known that N-methyl-D-aspartate receptor encephalitis (NMDARE) can be triggered by infectious encephalitis such as herpes simplex virus 1 encephalitis (HSE). However, the incidence of post-HSE NMDARE in Denmark is unknown. We reviewed literature cases and compared these to retrospectively identified cases of post-HSE NMDARE in Denmark, using a national cohort database of autoimmune encephalitis (AE) and two regional databases of infectious encephalitis patients. We identified 80 post-HSE NMDARE cases in the literature, 66% being children, who more often presented movement disorders, decreased consciousness, and sleep disturbances compared to adults. Eight patients with post-HSE NMDARE were identified from the national cohort database of AE, none being children. Forty-four HSE patients were identified from the regional infectious encephalitis databases. Of these, 16 (36%) fulfilled the Graus criteria for probable/definite NMDARE, and eight (18%) presented a prolonged/relapsing disease course. Ten (23%) were tested for AE during hospitalization. Six (14%) had leftover cerebrospinal fluid available for retrospective autoantibody testing. One out of these six patients (17%) harbored NMDARE antibodies. Thus, in total, nine post-HSE NMDARE patients have been identified in Denmark from 2009 to 2021. Comparing the adult Danish patients to the literature, Danish patients were older, but the clinical phenotype and paraclinical findings were similar. Overall, the incidence of adult post-HSE NMDARE in the Region of Southern Denmark was 0.17 per million people per year and only 7% of adult HSE patients in the region were diagnosed with post-HSE NMDARE. Our findings suggest that adult patients are still underdiagnosed and the absence of pediatric cases diagnosed with post-HSE NMDARE in Denmark is highly concerning. Full article
(This article belongs to the Special Issue Encephalitis and Viral Infection: Mechanisms and Therapies)
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19 pages, 4187 KiB  
Article
SARS-CoV-2 Spike Protein 1 Causes Aggregation of α-Synuclein via Microglia-Induced Inflammation and Production of Mitochondrial ROS: Potential Therapeutic Applications of Metformin
by Moon Han Chang, Jung Hyun Park, Hye Kyung Lee, Ji Young Choi and Young Ho Koh
Biomedicines 2024, 12(6), 1223; https://doi.org/10.3390/biomedicines12061223 - 31 May 2024
Viewed by 1240
Abstract
Abnormal aggregation of α-synuclein is the hallmark of neurodegenerative diseases, classified as α-synucleinopathies, primarily occurring sporadically. Their onset is associated with an interaction between genetic susceptibility and environmental factors such as neurotoxins, oxidative stress, inflammation, and viral infections. Recently, evidence has suggested an [...] Read more.
Abnormal aggregation of α-synuclein is the hallmark of neurodegenerative diseases, classified as α-synucleinopathies, primarily occurring sporadically. Their onset is associated with an interaction between genetic susceptibility and environmental factors such as neurotoxins, oxidative stress, inflammation, and viral infections. Recently, evidence has suggested an association between neurological complications in long COVID (sometimes referred to as ‘post-acute sequelae of COVID-19’) and α-synucleinopathies, but its underlying mechanisms are not completely understood. In this study, we first showed that SARS-CoV-2 Spike protein 1 (S1) induces α-synuclein aggregation associated with activation of microglial cells in the rodent model. In vitro, we demonstrated that S1 increases aggregation of α-synuclein in BE(2)M-17 dopaminergic neurons via BV-2 microglia-mediated inflammatory responses. We also identified that S1 directly affects aggregation of α-synuclein in dopaminergic neurons through increasing mitochondrial ROS, though only under conditions of sufficient α-Syn accumulation. In addition, we observed a synergistic effect between S1 and the neurotoxin MPP+ S1 treatment. Combined with a low dose of MPP+, it boosted α-synuclein aggregation and mitochondrial ROS production compared to S1 or the MPP+ treatment group. Furthermore, we evaluated the therapeutic effects of metformin. The treatment of metformin suppressed the S1-induced inflammatory response and α-synucleinopathy. Our findings demonstrate that S1 promotes α-synucleinopathy via both microglia-mediated inflammation and mitochondrial ROS, and they provide pathological insights, as well as a foundation for the clinical management of α-synucleinopathies and the onset of neurological symptoms after the COVID-19 outbreak. Full article
(This article belongs to the Special Issue Encephalitis and Viral Infection: Mechanisms and Therapies)
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