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Cells
Special Issues
Molecular Mechanisms of Immunity to Infectious Viruses
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Molecular Mechanisms of Immunity to Infectious Viruses

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (30 December 2023) | Viewed by 2794

Special Issue Editors

Dr. Marios Agelopoulos

E-Mail Website
Guest Editor
Center of Basic Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou St., 11527 Athens, Greece
Interests: viral infections; epigenome architecture and function; inducible gene expression programs; genomics; evolution of cis-acting elements
Dr. Tassos Georgakopoulos

E-Mail Website
Guest Editor
School of Medicine, University of Patras, Rio, Greece
Interests: viral infections; immune cell biology; gene expression programs; epigenetics; chromatin architecture
Dr. Dimitrios Vlachakis

E-Mail Website
Guest Editor
Genetics Laboratory, Biotechnology Department, Agricultural University of Athens, Athens, Greece
Interests: functional role of long non-coding RNAs; stress mechanisms and homeostasis via nuclear receptors; computational and molecular virology under the prisms of genetics; computational biology; precision medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

We are delighted to announce a Special Issue of Cells: "Molecular Mechanisms of Immunity to Infectious Viruses".

Viral infections dramatically impact human health and occasionally act as causal factors for morbidity and mortality among human populations that can lead to pandemic outbreaks. Immune responses are shaped as defense layers against viral life-cycle progression within human tissues. A hallmark of this function is the establishment of inducible expression programs. Much has been learned due to the advent of cell biology applications efficient in immunophenotyping and next-generation sequencing technologies, genomics applications, and computational biology tools applied to access the regulatory principles of gene expression, which can collectively illuminate the defense mechanisms that hosts utilize to combat viral infections. Advanced studies have characterized a plethora of cell types of the immune system and delineated diverse mechanistic principles, multiple layers of regulation, and cellular components, such as receptors, signal transduction cascades, transcriptional regulatory factors, chromatin complexes, and secreted effectors, committed in defense-specific responses at the cell- and tissue-level. Despite the essential knowledge that has emerged, it still remains challenging to comprehend how immune cells establish inducible gene-expression programs and shape efficient antiviral/defense responses within the heterogeneous 3D microenvironments of the human body. Hence, disentangling such perplexing phenomena is of paramount importance for an in-depth understanding of the mechanisms of human immunity, within and beyond the context of viral infections. 

For this Special Issue of Cells, research articles, research reports, and reviews focused on the molecular mechanisms of immunity to infectious viruses will be considered for publication.

Dr. Marios Agelopoulos
Dr. Tassos Georgakopoulos
Dr. Dimitrios Vlachakis
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. Cells is an international peer-reviewed open access semimonthly 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

  • viral infections
  • immune cell biology
  • gene expression programs
  • epigenetics
  • chromatin architecture
  • cis-regulatory elements
  • functional genomics
  • computational biology applications

Published Papers (2 papers)

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Research

19 pages, 4503 KiB  
Article
Oral Antiviral Defense: Saliva- and Beverage-like Hypotonicity Dynamically Regulate Formation of Membraneless Biomolecular Condensates of Antiviral Human MxA in Oral Epithelial Cells
by Pravin B. Sehgal, Huijuan Yuan, Anthony Centone and Susan V. DiSenso-Browne
Cells 2024, 13(7), 590; https://doi.org/10.3390/cells13070590 - 28 Mar 2024
Viewed by 883
Abstract
The oral mucosa represents a defensive barrier between the external environment and the rest of the body. Oral mucosal cells are constantly bathed in hypotonic saliva (normally one-third tonicity compared to plasma) and are repeatedly exposed to environmental stresses of tonicity, temperature, and [...] Read more.
The oral mucosa represents a defensive barrier between the external environment and the rest of the body. Oral mucosal cells are constantly bathed in hypotonic saliva (normally one-third tonicity compared to plasma) and are repeatedly exposed to environmental stresses of tonicity, temperature, and pH by the drinks we imbibe (e.g., hypotonic: water, tea, and coffee; hypertonic: assorted fruit juices, and red wines). In the mouth, the broad-spectrum antiviral mediator MxA (a dynamin-family large GTPase) is constitutively expressed in healthy periodontal tissues and induced by Type III interferons (e.g., IFN-λ1/IL-29). Endogenously induced human MxA and exogenously expressed human GFP-MxA formed membraneless biomolecular condensates in the cytoplasm of oral carcinoma cells (OECM1 cell line). These condensates likely represent storage granules in equilibrium with antivirally active dispersed MxA. Remarkably, cytoplasmic MxA condensates were exquisitely sensitive sensors of hypotonicity—the condensates in oral epithelium disassembled within 1–2 min of exposure of cells to saliva-like one-third hypotonicity, and spontaneously reassembled in the next 4–7 min. Water, tea, and coffee enhanced this disassembly. Fluorescence changes in OECM1 cells preloaded with calcein-AM (a reporter of cytosolic “macromolecular crowding”) confirmed that this process involved macromolecular uncrowding and subsequent recrowding secondary to changes in cell volume. However, hypertonicity had little effect on MxA condensates. The spontaneous reassembly of GFP-MxA condensates in oral epithelial cells, even under continuous saliva-like hypotonicity, was slowed by the protein-phosphatase-inhibitor cyclosporin A (CsA) and by the K-channel-blocker tetraethylammonium chloride (TEA); this is suggestive of the involvement of the volume-sensitive WNK kinase-protein phosphatase (PTP)-K-Cl cotransporter (KCC) pathway in the regulated volume decrease (RVD) during condensate reassembly in oral cells. The present study identifies a novel subcellular consequence of hypotonic stress in oral epithelial cells, in terms of the rapid and dynamic changes in the structure of one class of phase-separated biomolecular condensates in the cytoplasm—the antiviral MxA condensates. More generally, the data raise the possibility that hypotonicity-driven stresses likely affect other intracellular functions involving liquid–liquid phase separation (LLPS) in cells of the oral mucosa. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Immunity to Infectious Viruses)
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23 pages, 6077 KiB  
Article
Immunological Misfiring and Sex Differences/Similarities in Early COVID-19 Studies: Missed Opportunities of Making a Real IMPACT
by Aditi Bhargava and Johannes D. Knapp
Cells 2023, 12(22), 2591; https://doi.org/10.3390/cells12222591 - 8 Nov 2023
Cited by 3 | Viewed by 1385
Abstract
COVID-19-associated intensive care unit (ICU) admissions were recognized as critical health issues that contributed to morbidity and mortality in SARS-CoV-2-infected patients. Severe symptoms in COVID-19 patients are often accompanied by cytokine release syndrome. Here, we analyzed publicly available data from the Yale IMPACT [...] Read more.
COVID-19-associated intensive care unit (ICU) admissions were recognized as critical health issues that contributed to morbidity and mortality in SARS-CoV-2-infected patients. Severe symptoms in COVID-19 patients are often accompanied by cytokine release syndrome. Here, we analyzed publicly available data from the Yale IMPACT cohort to address immunological misfiring and sex differences in early COVID-19 patients. In 2020, SARS-CoV-2 was considered far more pathogenic and lethal than other circulating respiratory viruses, and the inclusion of SARS-CoV-2 negative patients in IMPACT cohorts confounds many findings. We ascertained the impact of several important biological variables such as days from symptom onset (DFSO); pre-existing risk factors, including obesity; and early COVID-19 treatments on significantly changed immunological measures in ICU-admitted COVID-19 patients that survived versus those that did not. Deceased patients had 19 unique measures that were not shared with ICU patients including increased granzyme-B-producing GzB+CD8+ T cells and interferon-γ. Male COVID-19 patients in ICU experienced many more changes in immunological and clinical measures than female ICU patients (25% vs. ~16%, respectively). A total of 13/124 measures including CCL5, CCL17, IL-18, IFNα2, Fractalkine, classical monocytes, T cells, and CD4Temra exhibited significant sex differences in female vs. male COVID-19 patients. A total of nine measures including IL-21, CCL5, and CD4Temra differed significantly between female and male healthy controls. Immunosuppressed patients experienced the most decreases in CD4Temra and CD8Tem cell numbers. None of the early COVID-19 treatments were effective in reducing levels of IL-6, a major component of the cytokine storm. Obesity (BMI >30) was the most impactful risk factor for COVID-19-related deaths and worst clinical outcomes. Our analysis highlights the contribution of biological sex, risk factors, and early treatments with respect to COVID-19-related ICU admission and progression to morbidity and mortality. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Immunity to Infectious Viruses)
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