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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 (15 March 2023) | Viewed by 32969

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Special Issue Editor

Prof. Dr. József Tőzsér

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Guest Editor

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary
Interests: viral replication; retroviruses; viral proteases; proteomics; viral gene therapy

Special Issue Information

Dear Colleagues,

Viral infections constitute a global burden on healthcare and are a leading cause of morbidity and mortality. In the past decade, the emergence and re-emergence of RNA viral infections caused by Ebola, Nipah, Flaviviruses, Dabie bandavirus, Influenza, and more recently, SARS-CoV-2, among others, have had devastating public health implications. Most of these pathogens are of zoonotic origin or are vector-borne, and given their evolvability and immense adaptive capacity, they continue to pose a global health threat. This is exemplified by recurring local outbreaks and pandemics. In this Special Issue, we focus on the broad range of emerging and re-emerging viral infections, with emphasis on human pathogens. Authors are welcome to contribute manuscripts that study or analyze the replication cycles and pathogenesis of these pathogens, or therapeutic and new advancements in vaccination strategies and molecular diagnostic techniques.

Prof. Dr. József Tőzsér
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.

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Keywords

Human viruses
Viral replication cycle
Viral entry to human cells
Zoonosis
Vector-born infections
Viral pathogenesis
Emerging diseases

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Published Papers (4 papers)

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Research

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19 pages, 3491 KiB

Open AccessArticle

Identification of SARS-CoV-2 Main Protease (Mpro) Cleavage Sites Using Two-Dimensional Electrophoresis and In Silico Cleavage Site Prediction

by Noémi Miltner, Gergő Kalló, Éva Csősz, Márió Miczi, Tibor Nagy, Mohamed Mahdi, János András Mótyán and József Tőzsér

Int. J. Mol. Sci. 2023, 24(4), 3236; https://doi.org/10.3390/ijms24043236 - 6 Feb 2023

Cited by 5 | Viewed by 3538

Abstract

The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a crucial role in its life cycle. The Mpro-mediated limited proteolysis of the viral polyproteins is necessary for the replication of the virus, and cleavage of the host proteins of the infected cells may also contribute to viral pathogenesis, such as evading the immune responses or triggering cell toxicity. Therefore, the identification of host substrates of the viral protease is of special interest. To identify cleavage sites in cellular substrates of SARS-CoV-2 Mpro, we determined changes in the HEK293T cellular proteome upon expression of the Mpro using two-dimensional gel electrophoresis. The candidate cellular substrates of Mpro were identified by mass spectrometry, and then potential cleavage sites were predicted in silico using NetCorona 1.0 and 3CLP web servers. The existence of the predicted cleavage sites was investigated by in vitro cleavage reactions using recombinant protein substrates containing the candidate target sequences, followed by the determination of cleavage positions using mass spectrometry. Unknown and previously described SARS-CoV-2 Mpro cleavage sites and cellular substrates were also identified. Identification of target sequences is important to understand the specificity of the enzyme, as well as aiding the improvement and development of computational methods for cleavage site prediction. Full article

(This article belongs to the Special Issue Newly Emerging or Re-emerging Viruses as a Potential Threat to Humans)

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Review

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13 pages, 759 KiB

Open AccessReview

Prospective Roles of Tumor Necrosis Factor-Alpha (TNF-α) in COVID-19: Prognosis, Therapeutic and Management

by Zarina Mohd Zawawi, Jeevanathan Kalyanasundram, Rozainanee Mohd Zain, Ravindran Thayan, Dayang Fredalina Basri and Wei Boon Yap

Int. J. Mol. Sci. 2023, 24(7), 6142; https://doi.org/10.3390/ijms24076142 - 24 Mar 2023

Cited by 41 | Viewed by 4971

Abstract

The coronavirus disease 2019 (COVID-19) became a worldwide concern at the beginning of 2020 and has affected millions. Several previous studies revealed the impact of the imbalanced innate immune response on the progression of COVID-19 and its disease outcomes. High levels of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukins are produced readily by innate immune cells to fight Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) infections. Nonetheless, cytokine-mediated inflammatory events are also linked to detrimental lung injury and respiratory failure, which can result in deaths among COVID-19 patients. TNF-α is amongst the early cytokines produced to mediate proinflammatory responses and enhance immune cell infiltration in response to SARS-CoV-2 infections. In COVID-19, TNF-α-mediated inflammation can cause detrimental tissue damage and gradually promotes lung fibrosis, which later results in pneumonia, pulmonary edema, and acute respiratory distress syndrome. This review, therefore, aims to deliberate the immunomodulatory roles of TNF-α in promoting inflammation and its relation with COVID-19 morbidity and mortality. In addition, this review also proposes the potential of TNF-α as a biomarker for the prognosis of severe COVID-19 and its related complications and as a molecular target for anti-TNF-α therapy. Full article

(This article belongs to the Special Issue Newly Emerging or Re-emerging Viruses as a Potential Threat to Humans)

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13 pages, 1089 KiB

Open AccessReview

Adaptive Immunity to Viruses: What Did We Learn from SARS-CoV-2 Infection?

by István Vályi-Nagy, Ferenc Uher, Éva Rákóczi and Zoltán Szekanecz

Int. J. Mol. Sci. 2022, 23(22), 13951; https://doi.org/10.3390/ijms232213951 - 12 Nov 2022

Cited by 8 | Viewed by 3411

Abstract

The SARS-CoV-2 virus causes various conditions, from asymptomatic infection to the fatal coronavirus disease 2019 (COVID-19). An intact immune system can overcome SARS-CoV-2 and other viral infections. Defective natural, mainly interferon I- and III-dependent, responses may lead to the spread of the virus to multiple organs. Adaptive B- and T-cell responses, including memory, highly influence the severity and outcome of COVID-19. With respect to B-cell immunity, germinal centre formation is delayed or even absent in the most severe cases. Extrafollicular low-affinity anti-SARS-CoV-2 antibody production will occur instead of specific, high-affinity antibodies. Helper and CD8+ cytotoxic T-cells become hyperactivated and then exhausted, leading to ineffective viral clearance from the body. The dysregulation of neutrophils and monocytes/macrophages, as well as lymphocyte hyperreactivity, might lead to the robust production of inflammatory mediators, also known as cytokine storm. Eventually, the disruption of this complex network of immune cells and mediators leads to severe, sometimes fatal COVID-19 or another viral disease. Full article

(This article belongs to the Special Issue Newly Emerging or Re-emerging Viruses as a Potential Threat to Humans)

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14 pages, 1872 KiB

Open AccessReview

Monkeypox: A New Threat?

by Dorota Kmiec and Frank Kirchhoff

Int. J. Mol. Sci. 2022, 23(14), 7866; https://doi.org/10.3390/ijms23147866 - 17 Jul 2022

Cited by 146 | Viewed by 20207

Abstract

The global vaccination programme against smallpox led to its successful eradication and averted millions of deaths. Monkeypox virus (MPXV) is a close relative of the Variola (smallpox) virus. Due to antigenic similarity, smallpox vaccines cross-protect against MPXV. However, over 70% of people living today were never vaccinated against smallpox. Symptoms of monkeypox (MPX) include fever, head- and muscle ache, lymphadenopathy and a characteristic rash that develops into papules, vesicles and pustules which eventually scab over and heal. MPX is less often fatal (case fatality rates range from <1% to up to 11%) than smallpox (up to 30%). MPXV is endemic in sub-Saharan Africa, infecting wild animals and causing zoonotic outbreaks. Exotic animal trade and international travel, combined with the increasing susceptibility of the human population due to halted vaccination, facilitated the spread of MPXV to new areas. The ongoing outbreak, with >10,000 cases in >50 countries between May and July 2022, shows that MPXV can significantly spread between people and may thus become a serious threat to public health with global consequences. Here, we summarize the current knowledge about this re-emerging virus, discuss available strategies to limit its spread and pathogenicity and evaluate its risk to the human population. Full article

(This article belongs to the Special Issue Newly Emerging or Re-emerging Viruses as a Potential Threat to Humans)

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