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Molecular Research of Viral Infections
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Molecular Research of Viral Infections

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: 10 June 2024 | Viewed by 9655

Special Issue Editors

Prof. Dr. Vladimir Chulanov

E-Mail Website
Guest Editor
Department of Infectious diseases, Sechenov University, 119048 Moscow, Russia
Interests: antivirals; chronic hepatitis B; hepatitis C virus; hepatitis D virus; epidemiology; molecular diagnostics; nanotechnologies; drug development
Dr. Dmitry Kostyushev

E-Mail Website
Guest Editor
Laboratory of Genetic Technologies, Sechenov First Moscow State Medical University, 119991 Moscow, Russia
Interests: antivirals; viral hepatitis; CRISPR/Cas; nanomedicine; drug delivery; transcriptomics; epitranscriptomics; cancer

Special Issue Information

Dear Colleagues,

Modern molecular approaches help to acquire new insights into the fundamental biology of viruses and pathogenesis of viral infections. Increasing our understanding of viral infections, the interaction of the virus with its host, virus-induced inflammation and cancers associated with viruses, may revolutionize available treatment and prevention options.

The Special Issue «Molecular Research of Viral Infections» focuses on the use of novel and emerging molecular technologies to unravel the complex interaction of viruses with the host and to understand basic viral biology with an emphasis on their potential practical use. Studies related to viruses on one of the following topics are invited:

  • Transcriptomics
  • Epitranscriptomics
  • Epigenomics
  • Proteomics
  • Mutations
  • Genetic diversity
  • Biomarkers
  • Structural biology of viruses
  • Viral replication
  • Virus-host interactions
  • Genetics and evolution of viruses
  • Molecular epidemiology
  • New models of viral infections
  • Virus-induced inflammation
  • Virus-induced cancerogenesis

Prof. Dr. Vladimir Chulanov
Dr. Dmitry Kostyushev
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. 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.

Published Papers (6 papers)

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Research

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18 pages, 6537 KiB  
Article
A Receptor Integrin β1 Promotes Infection of Avian Metapneumovirus Subgroup C by Recognizing a Viral Fusion Protein RSD Motif
by Yongqiu Cui, Siting Li, Weiyin Xu, Yeqiu Li, Jiali Xie, Dedong Wang, Jinshuo Guo, Jianwei Zhou, Xufei Feng, Lei Hou and Jue Liu
Int. J. Mol. Sci. 2024, 25(2), 829; https://doi.org/10.3390/ijms25020829 - 09 Jan 2024
Viewed by 854
Abstract
Avian metapneumovirus subgroup C (aMPV/C) causes respiratory diseases and egg dropping in chickens and turkeys, resulting in severe economic losses to the poultry industry worldwide. Integrin β1 (ITGB1), a transmembrane cell adhesion molecule, is present in various cells and mediates numerous viral infections. [...] Read more.
Avian metapneumovirus subgroup C (aMPV/C) causes respiratory diseases and egg dropping in chickens and turkeys, resulting in severe economic losses to the poultry industry worldwide. Integrin β1 (ITGB1), a transmembrane cell adhesion molecule, is present in various cells and mediates numerous viral infections. Herein, we demonstrate that ITGB1 is essential for aMPV/C infection in cultured DF-1 cells, as evidenced by the inhibition of viral binding by EDTA blockade, Arg-Ser-Asp (RSD) peptide, monoclonal antibody against ITGB1, and ITGB1 short interfering (si) RNA knockdown in cultured DF-1 cells. Simulation of the binding process between the aMPV/C fusion (F) protein and avian-derived ITGB1 using molecular dynamics showed that ITGB1 may be a host factor benefiting aMPV/C attachment or internalization. The transient expression of avian ITGB1-rendered porcine and feline non-permissive cells (DQ cells and CRFK cells, respectively) is susceptible to aMPV/C infection. Kinetic replication of aMPV/C in siRNA-knockdown cells revealed that ITGB1 plays an important role in aMPV/C infection at the early stage (attachment and internalization). aMPV/C was also able to efficiently infect human non-small cell lung cancer (A549) cells. This may be a consequence of the similar structures of both metapneumovirus F protein-specific motifs (RSD for aMPV/C and RGD for human metapneumovirus) recognized by ITGB1. Overexpression of avian-derived ITGB1 and human-derived ITGB1 in A549 cells enhanced aMPV/C infectivity. Taken together, this study demonstrated that ITGB1 acts as an essential receptor for aMPV/C attachment and internalization into host cells, facilitating aMPV/C infection. Full article
(This article belongs to the Special Issue Molecular Research of Viral Infections)
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12 pages, 2992 KiB  
Article
The Modification of the Illumina® CovidSeq™ Workflow for RSV Genomic Surveillance: The Genetic Variability of RSV during the 2022–2023 Season in Northwest Spain
by Carlos Davina-Nunez, Sonia Perez-Castro, Jorge Julio Cabrera-Alvargonzalez, Jhon Montano-Barrientos, Montse Godoy-Diz and Benito Regueiro
Int. J. Mol. Sci. 2023, 24(22), 16055; https://doi.org/10.3390/ijms242216055 - 07 Nov 2023
Viewed by 1332
Abstract
There is growing interest in the molecular surveillance of the Respiratory Syncytial Virus and the monitorization of emerging mutations that could impair the efficacy of antiviral prophylaxis and treatments. A simple, scalable protocol for viral nucleic acid enrichment could improve the surveillance of [...] Read more.
There is growing interest in the molecular surveillance of the Respiratory Syncytial Virus and the monitorization of emerging mutations that could impair the efficacy of antiviral prophylaxis and treatments. A simple, scalable protocol for viral nucleic acid enrichment could improve the surveillance of RSV. We developed a protocol for RSV-A and B amplification based on the Illumina CovidSeq workflow using an RSV primer panel. A total of 135 viral genomes were sequenced from nasopharyngeal samples through the optimization steps of this panel, while an additional 15 samples were used to test the final version. Full coverage of the G gene and over 95% of the coverage of the F gene, the target of the available RSV antivirals or monoclonal antibodies, were obtained. The F:K68N mutation, associated with decreased nirsevimab activity, was detected in our facility. Additionally, phylogenetic analysis showed several sublineages in the 2022–2023 influenza season in Europe. Our protocol allows for a simple and scalable simultaneous amplification of the RSV-A and B whole genome, increasing the yield of RSV sequencing and reducing costs. Its application would allow the world to be ready for the detection of arising mutations in relation to the widespread use of nirsevimab for RSV prevention. Full article
(This article belongs to the Special Issue Molecular Research of Viral Infections)
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17 pages, 2448 KiB  
Article
Pseudotyping Improves the Yield of Functional SARS-CoV-2 Virus-like Particles (VLPs) as Tools for Vaccine and Therapeutic Development
by Andrew J. Zak, Trang Hoang, Christine M. Yee, Syed M. Rizvi, Ponnandy Prabhu and Fei Wen
Int. J. Mol. Sci. 2023, 24(19), 14622; https://doi.org/10.3390/ijms241914622 - 27 Sep 2023
Viewed by 1127
Abstract
Virus-like particles (VLPs) have been proposed as an attractive tool in SARS-CoV-2 vaccine development, both as (1) a vaccine candidate with high immunogenicity and low reactogenicity and (2) a substitute for live virus in functional and neutralization assays. Though multiple SARS-CoV-2 VLP designs [...] Read more.
Virus-like particles (VLPs) have been proposed as an attractive tool in SARS-CoV-2 vaccine development, both as (1) a vaccine candidate with high immunogenicity and low reactogenicity and (2) a substitute for live virus in functional and neutralization assays. Though multiple SARS-CoV-2 VLP designs have already been explored in Sf9 insect cells, a key parameter ensuring VLPs are a viable platform is the VLP spike yield (i.e., spike protein content in VLP), which has largely been unreported. In this study, we show that the common strategy of producing SARS-CoV-2 VLPs by expressing spike protein in combination with the native coronavirus membrane and/or envelope protein forms VLPs, but at a critically low spike yield (~0.04–0.08 mg/L). In contrast, fusing the spike ectodomain to the influenza HA transmembrane domain and cytoplasmic tail and co-expressing M1 increased VLP spike yield to ~0.4 mg/L. More importantly, this increased yield translated to a greater VLP spike antigen density (~96 spike monomers/VLP) that more closely resembles that of native SARS-CoV-2 virus (~72–144 Spike monomers/virion). Pseudotyping further allowed for production of functional alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529) SARS-CoV-2 VLPs that bound to the target ACE2 receptor. Finally, we demonstrated the utility of pseudotyped VLPs to test neutralizing antibody activity using a simple, acellular ELISA-based assay performed at biosafety level 1 (BSL-1). Taken together, this study highlights the advantage of pseudotyping over native SARS-CoV-2 VLP designs in achieving higher VLP spike yield and demonstrates the usefulness of pseudotyped VLPs as a surrogate for live virus in vaccine and therapeutic development against SARS-CoV-2 variants. Full article
(This article belongs to the Special Issue Molecular Research of Viral Infections)
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8 pages, 700 KiB  
Communication
Performance of Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) Targeting the RNA Polymerase Gene for the Direct Detection of SARS-CoV2 in Nasopharyngeal Swabs
by Elias da Rosa Hoffmann, Lisiane da Rocha Balzan, Everton Inamine, Lisiane Rech Pancotto, Guilherme Gaboardi and Vlademir Vicente Cantarelli
Int. J. Mol. Sci. 2023, 24(17), 13056; https://doi.org/10.3390/ijms241713056 - 22 Aug 2023
Viewed by 880
Abstract
In 2020, a global pandemic caused by SARS-CoV-2 was declared. Different institutes proposed diagnostic molecular methods to detect the virus in clinical samples. This study aims to validate and standardize the use of a loop-mediated isothermal amplification (LAMP)-based methodology targeting the viral RP [...] Read more.
In 2020, a global pandemic caused by SARS-CoV-2 was declared. Different institutes proposed diagnostic molecular methods to detect the virus in clinical samples. This study aims to validate and standardize the use of a loop-mediated isothermal amplification (LAMP)-based methodology targeting the viral RP gene, as a faster and low-cost diagnostic method for SARS-CoV-2 infections. The results obtained with RT-LAMP (Reverse Transcriptase) were compared to the results of real-time polymerase chain reaction (RT-PCR) to assess its sensitivity and specificity. In total, 115 samples (nasopharyngeal samples) were used for detecting SARS-CoV-2 by RT-LAMP, with 43 positives and 72 negatives. The study showed a positive predictive value (PPV) of 90.7% and a negative predictive value (VPN) of 100%. The LAMP assay also demonstrated a high sensitivity of 90.7% and a specificity of 100% (confidence interval 77.9–97.4%) when using the lower detection limit of 40 copies/µL. The RT-LAMP described here has the potential to detect even the new variants of SARS-CoV-2, suggesting that it may not be significantly affected by gene mutations. The RT-LAMP targeting the RP viral region is faster and less expensive than other molecular approaches, making it an alternative for developing countries. Full article
(This article belongs to the Special Issue Molecular Research of Viral Infections)
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14 pages, 4677 KiB  
Article
PEMT Mediates Hepatitis C Virus-Induced Steatosis, Explains Genotype-Specific Phenotypes and Supports Virus Replication
by Mosleh Abomughaid, Enoch S. E. Tay, Russell Pickford, Chandra Malladi, Scott A. Read, Jens R. Coorssen, Brian S. Gloss, Jacob George and Mark W. Douglas
Int. J. Mol. Sci. 2023, 24(10), 8781; https://doi.org/10.3390/ijms24108781 - 15 May 2023
Cited by 1 | Viewed by 1482
Abstract
The hepatitis C virus (HCV) relies on cellular lipid pathways for virus replication and also induces liver steatosis, but the mechanisms involved are not clear. We performed a quantitative lipidomics analysis of virus-infected cells by combining high-performance thin-layer chromatography (HPTLC) and mass spectrometry, [...] Read more.
The hepatitis C virus (HCV) relies on cellular lipid pathways for virus replication and also induces liver steatosis, but the mechanisms involved are not clear. We performed a quantitative lipidomics analysis of virus-infected cells by combining high-performance thin-layer chromatography (HPTLC) and mass spectrometry, using an established HCV cell culture model and subcellular fractionation. Neutral lipid and phospholipids were increased in the HCV-infected cells; in the endoplasmic reticulum there was an ~four-fold increase in free cholesterol and an ~three-fold increase in phosphatidyl choline (p < 0.05). The increase in phosphatidyl choline was due to the induction of a non-canonical synthesis pathway involving phosphatidyl ethanolamine transferase (PEMT). An HCV infection induced expression of PEMT while knocking down PEMT with siRNA inhibited virus replication. As well as supporting virus replication, PEMT mediates steatosis. Consistently, HCV induced the expression of the pro-lipogenic genes SREBP 1c and DGAT1 while inhibiting the expression of MTP, promoting lipid accumulation. Knocking down PEMT reversed these changes and reduced the lipid content in virus-infected cells. Interestingly, PEMT expression was over 50% higher in liver biopsies from people infected with the HCV genotype 3 than 1, and three times higher than in people with chronic hepatitis B, suggesting that this may account for genotype-dependent differences in the prevalence of hepatic steatosis. PEMT is a key enzyme for promoting the accumulation of lipids in HCV-infected cells and supports virus replication. The induction of PEMT may account for virus genotype specific differences in hepatic steatosis. Full article
(This article belongs to the Special Issue Molecular Research of Viral Infections)
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Review

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20 pages, 1211 KiB  
Review
Antiviral Therapy of COVID-19
by Georgii Gudima, Ilya Kofiadi, Igor Shilovskiy, Dmitry Kudlay and Musa Khaitov
Int. J. Mol. Sci. 2023, 24(10), 8867; https://doi.org/10.3390/ijms24108867 - 16 May 2023
Cited by 11 | Viewed by 3337
Abstract
Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased [...] Read more.
Since the beginning of the COVID-19 pandemic, the scientific community has focused on prophylactic vaccine development. In parallel, the experience of the pharmacotherapy of this disease has increased. Due to the declining protective capacity of vaccines against new strains, as well as increased knowledge about the structure and biology of the pathogen, control of the disease has shifted to the focus of antiviral drug development over the past year. Clinical data on safety and efficacy of antivirals acting at various stages of the virus life cycle has been published. In this review, we summarize mechanisms and clinical efficacy of antiviral therapy of COVID-19 with drugs based on plasma of convalescents, monoclonal antibodies, interferons, fusion inhibitors, nucleoside analogs, and protease inhibitors. The current status of the drugs described is also summarized in relation to the official clinical guidelines for the treatment of COVID-19. In addition, here we describe innovative drugs whose antiviral effect is provided by antisense oligonucleotides targeting the SARS-CoV-2 genome. Analysis of laboratory and clinical data suggests that current antivirals successfully combat broad spectra of emerging strains of SARS-CoV-2 providing reliable defense against COVID-19. Full article
(This article belongs to the Special Issue Molecular Research of Viral Infections)
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