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Viral Infection in Humans: The Role of Immune System and Immunogenetics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Microbiology".

Deadline for manuscript submissions: closed (16 June 2021) | Viewed by 28355

Special Issue Editors


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Guest Editor
Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90134 Palermo, Italy
Interests: inflamm-aging; immunogenetics; nutritional interventions; positive biology; viral infections
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The COVID-19 outbreak has brought to light the necessity of being prepared for future pandemics.

To date, no vaccines exist against many viral infections, nor are there effective therapeutic strategies to eradicate the related diseases.

As demonstrated by recent discoveries regarding SARS-CoV-2, many viruses share similar mechanisms of action, although these can be different depending on age. As an example, the peculiarity of COVID-19 infection is that infants, children, and very old individuals, especially those that are longevous, show a sort of barrier against the virus or a surprising capacity to heal. An explanation could be found by analyzing the immune system mediators and studying the immunogenetic assets. What is their contribution?

This Special Issue will collect and present reviews and original studies in an attempt to find answers to this question proposed by the editors, summarizing and expanding upon the knowledge regarding the immune system and immunogenetic control in relation to responses to viral infections.

Papers could include and develop the following topics:

  • The role of immunogenetics in the control of viruses that can easily spread through the worldwide population;
  • The role of specific immune system mediators in viral diseases that can easily spread through the worldwide population;
  • The immunogenetic control of the production of immune system mediators and their role in the development of viruses that can easily spread through the worldwide population;
  • Case reports about interesting immunological responses to viruses that can easily spread through the worldwide population, as characterized from a molecular and biochemical point of view;

Dr. Anna Aiello
Dr. Giulia Accardi
Guest Editors

Manuscript Submission Information

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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

  • immune system
  • immunogenetics
  • viral infections
  • inflammation
  • pandemic infections

Published Papers (7 papers)

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Research

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14 pages, 1338 KiB  
Article
The MiR-320 Family Is Strongly Downregulated in Patients with COVID-19 Induced Severe Respiratory Failure
by Ruth P. Duecker, Elisabeth H. Adam, Sarah Wirtz, Lucia Gronau, Yascha Khodamoradi, Fabian J. Eberhardt, Helena Donath, Desiree Gutmann, Maria J. G. T. Vehreschild, Kai Zacharowski, Hermann Kreyenberg, Andreas G. Chiocchetti, Stefan Zielen and Ralf Schubert
Int. J. Mol. Sci. 2021, 22(19), 10351; https://doi.org/10.3390/ijms221910351 - 26 Sep 2021
Cited by 26 | Viewed by 3212
Abstract
A high incidence of thromboembolic events associated with high mortality has been reported in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections with respiratory failure. The present study characterized post-transcriptional gene regulation by global microRNA (miRNA) expression in relation to activated coagulation [...] Read more.
A high incidence of thromboembolic events associated with high mortality has been reported in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections with respiratory failure. The present study characterized post-transcriptional gene regulation by global microRNA (miRNA) expression in relation to activated coagulation and inflammation in 21 critically ill SARS-CoV-2 patients. The cohort consisted of patients with moderate respiratory failure (n = 11) and severe respiratory failure (n = 10) at an acute stage (day 0–3) and in the later course of the disease (>7 days). All patients needed supplemental oxygen and severe patients were defined by the requirement of positive pressure ventilation (intubation). Levels of D-dimers, activated partial thromboplastin time (aPTT), C-reactive protein (CRP), and interleukin (IL)-6 were significantly higher in patients with severe compared with moderate respiratory failure. Concurrently, next generation sequencing (NGS) analysis demonstrated increased dysregulation of miRNA expression with progression of disease severity connected to extreme downregulation of miR-320a, miR-320b and miR-320c. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed involvement in the Hippo signaling pathway, the transforming growth factor (TGF)-β signaling pathway and in the regulation of adherens junctions. The expression of all miR-320 family members was significantly correlated with CRP, IL-6, and D-dimer levels. In conclusion, our analysis underlines the importance of thromboembolic processes in patients with respiratory failure and emphasizes miRNA-320s as potential biomarkers for severe progressive SARS-CoV-2 infection. Full article
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23 pages, 4543 KiB  
Article
Anti-Influenza Activity of the Ribonuclease Binase: Cellular Targets Detected by Quantitative Proteomics
by Vera Ulyanova, Raihan Shah Mahmud, Alexander Laikov, Elena Dudkina, Maria Markelova, Ahmed Mostafa, Stephan Pleschka and Olga Ilinskaya
Int. J. Mol. Sci. 2020, 21(21), 8294; https://doi.org/10.3390/ijms21218294 - 5 Nov 2020
Cited by 8 | Viewed by 3390
Abstract
Unpredictable influenza pandemics, annual epidemics, and sporadic poultry-to-human avian influenza virus infections with high morbidity and mortality rates dictate a need to develop new antiviral approaches. Targeting cellular pathways and processes is a promising antiviral strategy shown to be effective regardless of viral [...] Read more.
Unpredictable influenza pandemics, annual epidemics, and sporadic poultry-to-human avian influenza virus infections with high morbidity and mortality rates dictate a need to develop new antiviral approaches. Targeting cellular pathways and processes is a promising antiviral strategy shown to be effective regardless of viral subtypes or viral evolution of drug-resistant variants. Proteomics-based searches provide a tool to reveal the druggable stages of the virus life cycle and to understand the putative antiviral mode of action of the drug(s). Ribonucleases (RNases) of different origins not only demonstrate antiviral effects that are mediated by the direct RNase action on viral and cellular RNAs but can also exert their impact by signal transduction modulation. To our knowledge, studies of the RNase-affected cell proteome have not yet been performed. To reveal cellular targets and explain the mechanisms underlying the antiviral effect employed by the small extra-cellular ribonuclease of Bacillus pumilus (binase) both in vitro and in vivo, qualitative shotgun and quantitative targeted proteomic analyses of the influenza A virus (IAV) H1N1pdm09-infected A549 cells upon binase treatment were performed. We compared proteomes of mock-treated, binase-treated, virus-infected, and virus-infected binase-treated cells to determine the proteins affected by IAV and/or binase. In general, IAV demonstrated a downregulating strategy towards cellular proteins, while binase had an upregulating effect. With the help of bioinformatics approaches, coregulated cellular protein sets were defined and assigned to their biological function; a possible interconnection with the progression of viral infection was conferred. Most of the proteins downregulated by IAV (e.g., AKR1B1, AKR1C1, CCL5, PFN1, RAN, S100A4, etc.) belong to the processes of cellular metabolism, response to stimulus, biological regulation, and cellular localization. Upregulated proteins upon the binase treatment (e.g., AKR1B10, CAP1, HNRNPA2B1, PFN1, PPIA, YWHAB, etc.) are united by the processes of biological regulation, cellular localization, and immune and metabolic processes. The antiviral activity of binase against IAV was expressed by the inversion of virus-induced proteomic changes, resulting in the inhibition of virus-associated processes, including nuclear ribonucleoprotein export (NCL, NPM1, Nup205, and Bax proteins involved) and cytoskeleton remodeling (RDX, PFN1, and TUBB) induced by IAV at the middle stage of single-cycle infection in A549 cells. Modulation of the immune response could be involved as well. Overall, it seems possible that binase exerts its antiviral effects in multiple ways. Full article
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Review

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34 pages, 2929 KiB  
Review
Evasion of the Host Immune Response by Betaherpesviruses
by Daniel G. Sausen, Kirstin M. Reed, Maimoona S. Bhutta, Elisa S. Gallo and Ronen Borenstein
Int. J. Mol. Sci. 2021, 22(14), 7503; https://doi.org/10.3390/ijms22147503 - 13 Jul 2021
Cited by 11 | Viewed by 3738
Abstract
The human immune system boasts a diverse array of strategies for recognizing and eradicating invading pathogens. Human betaherpesviruses, a highly prevalent subfamily of viruses, include human cytomegalovirus (HCMV), human herpesvirus (HHV) 6A, HHV-6B, and HHV-7. These viruses have evolved numerous mechanisms for evading [...] Read more.
The human immune system boasts a diverse array of strategies for recognizing and eradicating invading pathogens. Human betaherpesviruses, a highly prevalent subfamily of viruses, include human cytomegalovirus (HCMV), human herpesvirus (HHV) 6A, HHV-6B, and HHV-7. These viruses have evolved numerous mechanisms for evading the host response. In this review, we will highlight the complex interplay between betaherpesviruses and the human immune response, focusing on protein function. We will explore methods by which the immune system first responds to betaherpesvirus infection as well as mechanisms by which viruses subvert normal cellular functions to evade the immune system and facilitate viral latency, persistence, and reactivation. Lastly, we will briefly discuss recent advances in vaccine technology targeting betaherpesviruses. This review aims to further elucidate the dynamic interactions between betaherpesviruses and the human immune system. Full article
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23 pages, 2470 KiB  
Review
Intracellular Redox-Modulated Pathways as Targets for Effective Approaches in the Treatment of Viral Infection
by Alessandra Fraternale, Carolina Zara, Marta De Angelis, Lucia Nencioni, Anna Teresa Palamara, Michele Retini, Tomas Di Mambro, Mauro Magnani and Rita Crinelli
Int. J. Mol. Sci. 2021, 22(7), 3603; https://doi.org/10.3390/ijms22073603 - 30 Mar 2021
Cited by 34 | Viewed by 3727
Abstract
Host-directed therapy using drugs that target cellular pathways required for virus lifecycle or its clearance might represent an effective approach for treating infectious diseases. Changes in redox homeostasis, including intracellular glutathione (GSH) depletion, are one of the key events that favor virus replication [...] Read more.
Host-directed therapy using drugs that target cellular pathways required for virus lifecycle or its clearance might represent an effective approach for treating infectious diseases. Changes in redox homeostasis, including intracellular glutathione (GSH) depletion, are one of the key events that favor virus replication and contribute to the pathogenesis of virus-induced disease. Redox homeostasis has an important role in maintaining an appropriate Th1/Th2 balance, which is necessary to mount an effective immune response against viral infection and to avoid excessive inflammatory responses. It is known that excessive production of reactive oxygen species (ROS) induced by viral infection activates nuclear factor (NF)-kB, which orchestrates the expression of viral and host genes involved in the viral replication and inflammatory response. Moreover, redox-regulated protein disulfide isomerase (PDI) chaperones have an essential role in catalyzing formation of disulfide bonds in viral proteins. This review aims at describing the role of GSH in modulating redox sensitive pathways, in particular that mediated by NF-kB, and PDI activity. The second part of the review discusses the effectiveness of GSH-boosting molecules as broad-spectrum antivirals acting in a multifaceted way that includes the modulation of immune and inflammatory responses. Full article
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27 pages, 843 KiB  
Review
The Role of Immunogenetics in COVID-19
by Fanny Pojero, Giuseppina Candore, Calogero Caruso, Danilo Di Bona, David A. Groneberg, Mattia E. Ligotti, Giulia Accardi and Anna Aiello
Int. J. Mol. Sci. 2021, 22(5), 2636; https://doi.org/10.3390/ijms22052636 - 5 Mar 2021
Cited by 22 | Viewed by 5120
Abstract
Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to a life-threatening disease associated with cytokine storm, multiorgan and respiratory failure. The molecular mechanism behind such variability is still under [...] Read more.
Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to a life-threatening disease associated with cytokine storm, multiorgan and respiratory failure. The molecular mechanism behind such variability is still under investigation. Several pieces of experimental evidence suggest that genetic variants influencing the onset, maintenance and resolution of the immune response may be fundamental in predicting the evolution of the disease. The identification of genetic variants behind immune system reactivity and function in COVID-19 may help in the elaboration of personalized therapeutic strategies. In the frenetic look for universally shared treatment plans, those genetic variants that are common to other diseases/models may also help in addressing future research in terms of drug repurposing. In this paper, we discuss the most recent updates about the role of immunogenetics in determining the susceptibility to and the history of SARS-CoV-2 infection. We propose a narrative review of available data, speculating about lessons that we have learnt from other viral infections and immunosenescence, and discussing what kind of aspects of research should be deepened in order to improve our knowledge of how host genetic variability impacts the outcome for COVID-19 patients. Full article
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13 pages, 3463 KiB  
Review
Epstein–Barr Virus-Positive Mucocutaneous Ulcer: A Unique and Curious Disease Entity
by Tomoka Ikeda, Yuka Gion, Yoshito Nishimura, Midori Filiz Nishimura, Tadashi Yoshino and Yasuharu Sato
Int. J. Mol. Sci. 2021, 22(3), 1053; https://doi.org/10.3390/ijms22031053 - 21 Jan 2021
Cited by 27 | Viewed by 5526
Abstract
Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in 2010. EBVMCU is a unifocal mucosal or cutaneous ulcer that often occurs after local trauma in patients with immunosuppression; the patients generally have a good prognosis. It is histologically [...] Read more.
Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in 2010. EBVMCU is a unifocal mucosal or cutaneous ulcer that often occurs after local trauma in patients with immunosuppression; the patients generally have a good prognosis. It is histologically characterized by proliferating EBV-positive atypical B cells accompanied by ulcers. On the basis of conventional pathologic criteria, EBVMCU may be misdiagnosed as EBV-positive diffuse large B-cell lymphoma or other lymphomas. However, its prognosis differs from that of EBV-associated lymphomas, in that patients with EBVMCU frequently show spontaneous regression or complete remission without chemotherapy. Therefore, EBVMCU is now recognized as a low-grade malignancy or a pseudo-malignant lesion. Avoiding unnecessary chemotherapy by distinguishing EBVMCU from other EBV-associated lymphomas will reduce the burden and unnecessary harm on patients. On the basis of these facts, EBVMCU was first described as a new clinicopathological entity by the World Health Organization in 2017. In this review, we discuss the clinicopathological characteristics of previously reported EBVMCU cases, while focusing on up-to-date clinical, pathological, and genetic aspects. Full article
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14 pages, 619 KiB  
Review
Cardiovascular Disease and SARS-CoV-2: the Role of Host Immune Response Versus Direct Viral Injury
by Federico Biscetti, Maria Margherita Rando, Elisabetta Nardella, Andrea Leonardo Cecchini, Piergiorgio Bruno, Raffaele Landolfi and Andrea Flex
Int. J. Mol. Sci. 2020, 21(21), 8141; https://doi.org/10.3390/ijms21218141 - 30 Oct 2020
Cited by 5 | Viewed by 2371
Abstract
The 2019 novel coronavirus [2019-nCoV], which started to spread from December 2019 onwards, caused a global pandemic. Besides being responsible for the severe acute respiratory syndrome 2 [SARS-CoV-2], the virus can affect other organs causing various symptoms. A close relationship between SARS-CoV-2 and [...] Read more.
The 2019 novel coronavirus [2019-nCoV], which started to spread from December 2019 onwards, caused a global pandemic. Besides being responsible for the severe acute respiratory syndrome 2 [SARS-CoV-2], the virus can affect other organs causing various symptoms. A close relationship between SARS-CoV-2 and the cardiovascular system has been shown, demonstrating an epidemiological linkage between SARS-CoV-2 and cardiac injury. There are emerging data regarding possible direct myocardial damage by 2019-nCoV. In this review, the most important available evidences will be discussed to clarify the precise mechanisms of cardiovascular injury in SARS-CoV-2 patients, even if further researches are needed. Full article
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