Molecular Mechanisms of Viral Infections

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 May 2025 | Viewed by 3044

Special Issue Editors


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Guest Editor
Laboratory of Biology, Medical School, Democritus University of Thrace, 68100 Alexandroupolis, Greece
Interests: virus-host interactions; virome; viral evolution
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: oncogenic viruses; virus-host interactions; viral genome editing; viral evolution
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Viruses are complex biological entities that have evolved intricate molecular mechanisms to invade host cells in order to replicate and spread efficiently. Understanding the molecular mechanisms of viral infections is essential for unraveling the dynamic interactions between viruses and host cells, elucidating the pathogenesis of viral diseases, and devising effective antiviral strategies. This Special Issue delves into the fundamental principles governing virus–host interactions, the key molecular events facilitating virus entry, replication, and spread, and the implications of these interactions in disease. By dissecting the molecular intricacies of viral infections, researchers aim to develop innovative therapeutics and vaccines to combat viral infections and mitigate their global impact on public health.

The aim of this Special Issue is to better understand the molecular mechanisms that are implicated in viral infections. We welcome submissions of research articles and reviews focused on molecular mechanisms unraveling the dynamic interactions between viruses and host cells. This Special Issue of Biomolecules focuses on mechanisms such as viral entry, replication, assembly, egress, pathogenesis, and diversity and antiviral strategies, vaccine candidates, host responses, and signaling and development of new tools to study the above mechanisms in order to align with expert views, state of the art, and recent advancements in the field of viral infections.

Dr. Ioannis Karakasiliotis
Dr. Christine Kottaridi
Guest Editors

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Keywords

  • viral replication
  • virus evolution
  • immune response
  • antiviral strategies virus
  • infection
  • pathogenesis
  • virulence

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Published Papers (3 papers)

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Research

15 pages, 4617 KiB  
Article
Human Coronavirus 229E Uses Clathrin-Mediated Endocytosis as a Route of Entry in Huh-7 Cells
by Sabina Andreu, Inés Ripa, José Antonio López-Guerrero and Raquel Bello-Morales
Biomolecules 2024, 14(10), 1232; https://doi.org/10.3390/biom14101232 - 29 Sep 2024
Viewed by 791
Abstract
Human coronavirus 229E (HCoV-229E) is an endemic coronavirus responsible for approximately one-third of “common cold” cases. To infect target cells, HCoV-229E first binds to its receptor on the cell surface and then can follow different pathways, entering by direct fusion or by taking [...] Read more.
Human coronavirus 229E (HCoV-229E) is an endemic coronavirus responsible for approximately one-third of “common cold” cases. To infect target cells, HCoV-229E first binds to its receptor on the cell surface and then can follow different pathways, entering by direct fusion or by taking advantage of host cell mechanisms such as endocytosis. Based on the role of clathrin, the process can be classified into clathrin-dependent or -independent endocytosis. This study characterizes the role of clathrin-mediated endocytosis (CME) in HCoV-229E infection of the human hepatoma cell line Huh-7. Using specific CME inhibitory drugs, we demonstrated that blocking CME significantly reduces HCoV-229E infection. Additionally, CRISPR/Cas9-mediated knockout of the µ subunit of adaptor protein complex 2 (AP-2) further corroborated the role of CME, as KOs showed over a 50% reduction in viral infection. AP-2 plays an important role in clathrin recruitment and the maturation of clathrin-coated vesicles. Our study also confirmed that in Huh-7 cells, HCoV-229E requires endosomal acidification for successful entry, as viral entry decreased when treated with lysomotropic agents. Furthermore, the colocalization of HCoV-229E with early endosome antigen 1 (EEA-1), only present in early endosomes, suggested that the virus uses an endosomal route for entry. These findings highlight, for the first time, the role of CME in HCoV-229E infection and confirm previous data of the use of the endosomal route at a low pH in the experimental cell model Huh-7. Our results provide new insights into the mechanisms of entry of HCoV-229E and provide a new basis for the development of targeted antiviral therapies. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Viral Infections)
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17 pages, 2964 KiB  
Article
Biomolecular Dynamics of Nitric Oxide Metabolites and HIF1α in HPV Infection
by Clara Matei, Ilinca Nicolae, Madalina Irina Mitran, Cristina Iulia Mitran, Corina Daniela Ene, Gheorghe Nicolae, Simona Roxana Georgescu and Mircea Tampa
Biomolecules 2024, 14(9), 1172; https://doi.org/10.3390/biom14091172 - 18 Sep 2024
Viewed by 640
Abstract
Introduction: Viral infections cause oxygen deprivation, leading to hypoxia or anoxia in certain tissues. The limitation of mitochondrial respiration is one of the major events during hypoxia that induces alternative metabolic activities and increased levels of certain biomolecules such as nitric oxide (NO) [...] Read more.
Introduction: Viral infections cause oxygen deprivation, leading to hypoxia or anoxia in certain tissues. The limitation of mitochondrial respiration is one of the major events during hypoxia that induces alternative metabolic activities and increased levels of certain biomolecules such as nitric oxide (NO) metabolites. In this study, we aimed to investigate the role of NO metabolites and hypoxia in HPV infection. Materials and Methods: We included 36 patients with palmoplantar warts and 36 healthy subjects and performed serum determinations of NO metabolites (direct nitrite, total nitrite, nitrate, and 3-nitrotyrosine) and HIF1α, a marker of hypoxia. Results: We found elevated serum levels in NO metabolites and HIF1α, and decreased direct nitrite/nitrate ratios in patients with warts versus controls. Additionally, we identified statistically significant positive correlations between NO metabolites and HIF1α levels, except for 3-nitrotyrosine. Conclusions: Our findings show that HPV infection causes hypoxia and alterations in NO metabolism and suggest a link between wart development and cellular stress. Our research could provide new insights for a comprehensive understanding of the pathogenesis of cutaneous HPV infections. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Viral Infections)
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24 pages, 17687 KiB  
Article
Secondary Envelopment of Human Cytomegalovirus Is a Fast Process Utilizing the Endocytic Compartment as a Major Membrane Source
by Tim Bergner, Laura Cortez Rayas, Gesa Freimann, Clarissa Read and Jens von Einem
Biomolecules 2024, 14(9), 1149; https://doi.org/10.3390/biom14091149 - 12 Sep 2024
Viewed by 798
Abstract
Secondary envelopment of the human cytomegalovirus (HCMV) is a critical but not well-understood process that takes place at the cytoplasmic viral assembly complex (cVAC) where nucleocapsids acquire their envelope by budding into cellular membranes containing viral glycoproteins. Previous studies presented controversial results regarding [...] Read more.
Secondary envelopment of the human cytomegalovirus (HCMV) is a critical but not well-understood process that takes place at the cytoplasmic viral assembly complex (cVAC) where nucleocapsids acquire their envelope by budding into cellular membranes containing viral glycoproteins. Previous studies presented controversial results regarding the composition of the viral envelope, suggesting trans-Golgi and endosomal origins, as well as intersections with the exosomal and endocytic pathways. Here, we investigated the role of endocytic membranes for the secondary envelopment of HCMV by using wheat germ agglutinin (WGA) pulse labeling to label glycoproteins at the plasma membrane and to follow their trafficking during HCMV infection by light microscopy and transmission electron microscopy (TEM). WGA labeled different membrane compartments within the cVAC, including early endosomes, multivesicular bodies, trans-Golgi, and recycling endosomes. Furthermore, TEM analysis showed that almost 90% of capsids undergoing secondary envelopment and 50% of enveloped capsids were WGA-positive within 90 min. Our data reveal extensive remodeling of the endocytic compartment in the late stage of HCMV infection, where the endocytic compartment provides an optimized environment for virion morphogenesis and serves as the primary membrane source for secondary envelopment. Furthermore, we show that secondary envelopment is a rapid process in which endocytosed membranes are transported from the plasma membrane to the cVAC within minutes to be utilized by capsids for envelopment. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Viral Infections)
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