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The Evolution, Genetics and Pathogenesis of Viruses

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: 30 October 2025 | Viewed by 10206

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Guest Editor
Instytut Chemii Bioorganicznej Polskiej Akademii Nauk, 61-704 Poznan, Poland
Interests: RNA/DNA structure; G-quadruplex; influenza virus; structural biology; RNA/DNA thermodynamic
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Special Issue Information

Dear Colleagues, 

Viruses are an important research subject around the world because of their serious threat to humanity. The current COVID-19 pandemic is unprecedented with regard to the rate of spread and mortality rate. Moreover, a lack of knowledge of the mode of transmission and spread of the virus makes it difficult to fight the infection. Overall, the pandemic potential of viruses is a result of the high variability of their genome and is correlated with their pathogenicity, replication, and growth kinetics. It is known that the nature of the viral genome (RNA or DNA) plays an important role in its genetics. Therefore, a detailed analysis of the viral genetic material, including its structure, function–structure relationships, and virus–host interactions allow us to provide new insights into viral infections. In the future, it also might be useful for the determination of potential antiviral targets within viral genomes, as well as for designing and developing new therapeutics.

Dr. Marta Szabat
Guest Editor

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Keywords

  • viruses
  • genome structure
  • viral RNA/DNA
  • replication viral cycle
  • recombination
  • viral infection
  • antiviral agents

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Published Papers (7 papers)

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Research

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20 pages, 2782 KiB  
Article
A Comparative Genomic Analysis of Epstein–Barr Virus Strains with a Focus on EBV2 Variability
by Ana Catalina Blazquez, María Dolores Fellner, Mario Alejandro Lorenzetti and María Victoria Preciado
Int. J. Mol. Sci. 2025, 26(6), 2708; https://doi.org/10.3390/ijms26062708 - 17 Mar 2025
Viewed by 635
Abstract
Most genomic studies on Epstein–Barr virus variability have focused on the geographic and pathological associations of EBV1 genomes. In contrast, the variability of EBV2 genomes has been less explored, mainly due to their restricted geographic circulation and the lesser number of sequenced EBV2 [...] Read more.
Most genomic studies on Epstein–Barr virus variability have focused on the geographic and pathological associations of EBV1 genomes. In contrast, the variability of EBV2 genomes has been less explored, mainly due to their restricted geographic circulation and the lesser number of sequenced EBV2 isolates. In this study, we sequenced and analyzed twenty-eight EBV1 and ten EBV2 genomes and a potential recombinant from Argentina, which were combined with two-hundred-and-thirty-nine downloaded complete genomes from other geographic regions, to produce an initial multi-sample.vcf file comprising 278 EBV genomes. In this context, we identified 1093/4541 positions in the viral genome that contribute to variability between viral types, mainly located in the EBNA2 and EBNA3 family of genes and the adjacent BZLF1, BZLF2, and BLLF1 genes. We further described that this variability exhibits distinct patterns across Africa, South America, and Southeast Asia. Compared to EBV1 genomes, EBV2 genomes showed fewer variable positions relative to their reference genome (Wilcoxon test, p = 0.0001). Principal component analysis revealed that EBV2 genomes from Southeast Asia segregate independently from those from South America (Wilcoxon test, Bonferroni correction; p = 1.1 × 10−7) and Africa (Wilcoxon test, Bonferroni correction; p = 2.6 × 10−9). Additionally, we identified those precise variable positions with geographic segregation strength: 1135/3666 in EBV1 and 380/3276 in EBV2. Furthermore, the distribution of variable positions along the genome disclosed a close relation for EBV2 isolates from Africa and South America as compared to isolates from Southeast Asia. Although our analysis is limited to EBV2 genomes isolated from three geographic regions, this was, to the best of our knowledge, the first study to comprehensively characterize the geographic variability of the complete EBV2 genome. These findings underscore the geographic and genetic diversity of EBV2 genomes and contribute to understanding the EBV’s evolutionary dynamics and potential regional adaptations. This research enhances our understanding of EBV2 genomic variability, supporting future epidemiological studies and advancing the knowledge base for targeted treatments and vaccine development for EBV-associated diseases. Full article
(This article belongs to the Special Issue The Evolution, Genetics and Pathogenesis of Viruses)
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11 pages, 2338 KiB  
Communication
Viral Network Analyzer (VirNA): A Novel Minimum Spanning Networks Algorithm for Investigating Viral Evolution
by Giorgia Mazzotti, Luca Bianco, Enrico Lavezzo, Martina Bado, Stefano Toppo and Paolo Fontana
Int. J. Mol. Sci. 2025, 26(5), 2008; https://doi.org/10.3390/ijms26052008 - 25 Feb 2025
Viewed by 536
Abstract
Next Generation Sequencing technologies are essential in public health surveillance for tracking pathogen evolution, spread, and the emergence of new variants. However, the extensive sequencing of viral genomes during recent pandemics has highlighted the limitations of traditional molecular phylogenetic algorithms in capturing fine-grained [...] Read more.
Next Generation Sequencing technologies are essential in public health surveillance for tracking pathogen evolution, spread, and the emergence of new variants. However, the extensive sequencing of viral genomes during recent pandemics has highlighted the limitations of traditional molecular phylogenetic algorithms in capturing fine-grained evolutionary details when analyzed sequences are highly similar and datasets are large-scale. VirNA (Viral Network Analyzer) addresses this challenge by reconstructing detailed mutation patterns and tracing pathogen evolutionary routes in specific geographical regions through Minimum Spanning Networks. It enables users to analyze thousands of sequences, generating networks where nodes represent genomic sequences linked to their metadata, while edges represent potential evolutionary pathways. VirNA is a powerful tool for analyzing large, high-quality datasets, providing detailed insights into rapid pathogen evolution over short time periods, with potential applications in pandemic surveillance. Full article
(This article belongs to the Special Issue The Evolution, Genetics and Pathogenesis of Viruses)
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12 pages, 2073 KiB  
Communication
Establishment of a Panel of Human Cell Lines to Identify Cellular Receptors Used by Enteroviruses to Infect Cells
by Anastasiia O. Sosnovtseva, Thi Hoa Le, Dmitry S. Karpov, Pavel O. Vorobyev, Yana D. Gumennaya, Olga N. Alekseeva, Peter M. Chumakov and Anastasia V. Lipatova
Int. J. Mol. Sci. 2025, 26(3), 923; https://doi.org/10.3390/ijms26030923 - 22 Jan 2025
Viewed by 1624
Abstract
Non-pathogenic natural and recombinant strains of human Enteroviruses are the subject of ongoing study with some strains having been approved for use as anticancer agents. The efficacy of oncolytic virotherapy depends upon identifying the receptor utilized by a specific strain for cell entry, [...] Read more.
Non-pathogenic natural and recombinant strains of human Enteroviruses are the subject of ongoing study with some strains having been approved for use as anticancer agents. The efficacy of oncolytic virotherapy depends upon identifying the receptor utilized by a specific strain for cell entry, and the presence of this receptor on the surface of cancer cells. Accordingly, a rapid and straightforward approach to determining the enteroviral receptors is necessary for developing an effective patient-specific, virus-based cancer therapy. To this end, we created a panel of seven lines with double knockouts on the background of the HEK293T cell line, which lacks the IFNAR1 gene. In these lines, the main viral receptor genes, including PVR, CXADR, CD55, ITGA2, SCARB2, ICAM1, and FCGRT, were knocked out using the CRISPR/Cas9 system. The panel of lines was validated on twelve different Enteroviruses types, providing a basis for studying the molecular mechanisms of enterovirus entry into cells, and for developing new therapeutic strains. Full article
(This article belongs to the Special Issue The Evolution, Genetics and Pathogenesis of Viruses)
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15 pages, 44296 KiB  
Article
Phylogenetic Analysis of Porcine Epidemic Diarrhea Virus (PEDV) during 2020–2022 and Isolation of a Variant Recombinant PEDV Strain
by Qianling Peng, Ping Fu, Yutong Zhou, Yifei Lang, Shan Zhao, Yiping Wen, Yiping Wang, Rui Wu, Qin Zhao, Senyan Du, Sanjie Cao, Xiaobo Huang and Qigui Yan
Int. J. Mol. Sci. 2024, 25(20), 10878; https://doi.org/10.3390/ijms252010878 - 10 Oct 2024
Cited by 3 | Viewed by 1977
Abstract
Porcine epidemic diarrhea (PED) is an acute, highly contagious, and infectious disease caused by porcine epidemic diarrhea virus (PEDV). PEDV can affect pigs of all ages, with 50~100% mortality in neonatal piglets and substantial economic losses in the swine industry. In the present [...] Read more.
Porcine epidemic diarrhea (PED) is an acute, highly contagious, and infectious disease caused by porcine epidemic diarrhea virus (PEDV). PEDV can affect pigs of all ages, with 50~100% mortality in neonatal piglets and substantial economic losses in the swine industry. In the present study, 347 fecal and intestinal samples were collected from seven regions in China during 2020–2022. A comprehensive molecular investigation of the spike (S) gene of PEDV strains was carried out, which included phylogenetic analysis of the obtained PEDV sequences. Epidemiological surveillance data indicate that the GIIc subgroup strains are widely distributed among pigs. A PEDV strain was successfully isolated from positive small intestine samples and identified through RT-PCR detection using specific N gene primers of PEDV, indirect immunofluorescence assay (IFA), TEM analysis, genome sequencing, and full-length S gene analysis, named PEDV/SC/2022. RDP and SimPlot analysis showed that the isolate originated from the recombination of PEDV/AH2012 and PEDV/AJ1102. In conclusion, our findings contribute to the current understanding of PEDV epidemiology and provide valuable information for the control of PED outbreaks in China. Full article
(This article belongs to the Special Issue The Evolution, Genetics and Pathogenesis of Viruses)
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13 pages, 73363 KiB  
Article
Phylogenetic Analysis and Serological Investigation of Porcine Circovirus Indicates Frequent Infection with Various Subtypes
by Qianling Peng, Jiqiang Shi, Yifei Lang, Yulan Zhu, Xiaobo Huang, Sanjie Cao, Qigui Yan and Shan Zhao
Int. J. Mol. Sci. 2023, 24(21), 15850; https://doi.org/10.3390/ijms242115850 - 1 Nov 2023
Cited by 4 | Viewed by 2100
Abstract
Porcine circoviruses (PCVs) are notorious for triggering severe diseases in pigs and causing serious economic losses to the swine industry. In the present study, we undertook a comprehensive approach for the investigation of PCV prevalence, including the phylogenetic analysis of obtained PCV sequences, [...] Read more.
Porcine circoviruses (PCVs) are notorious for triggering severe diseases in pigs and causing serious economic losses to the swine industry. In the present study, we undertook a comprehensive approach for the investigation of PCV prevalence, including the phylogenetic analysis of obtained PCV sequences, the determination of major circulating genotypes and serological screening based on different recombinant Cap proteins with specific immunoreactivity. Epidemiological surveillance data indicate that PCV2d and PCV3a are widely distributed in Southwest China, while PCV4 has only sporadic circulation. Meanwhile, serological investigations showed high PCV2 antibody positivity in collected serum samples (>50%), followed by PCV4 (nearly 50%) and PCV3 (30–35%). The analysis supports different circulation patterns of PCV2, PCV3 and PCV4 and illustrates the PCV2/PCV3 genetic evolution characteristics on a nationwide basis. Taken together, our findings add up to the current understanding of PCV epidemiology and provide new tools and insight for PCV antiviral intervention. Full article
(This article belongs to the Special Issue The Evolution, Genetics and Pathogenesis of Viruses)
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Review

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17 pages, 1421 KiB  
Review
Comparative Review of the Conserved UL24 Protein Family in Herpesviruses
by Odelia Orbaum-Harel and Ronit Sarid
Int. J. Mol. Sci. 2024, 25(20), 11268; https://doi.org/10.3390/ijms252011268 - 19 Oct 2024
Cited by 1 | Viewed by 1348
Abstract
The UL24 protein family, conserved across all subfamilies of Orthoherpesviridae, plays diverse and significant roles in viral replication, host–virus interactions and pathogenesis. Understanding the molecular mechanisms and interactions of UL24 proteins is key to unraveling the complex interplay between herpesviruses and their hosts. [...] Read more.
The UL24 protein family, conserved across all subfamilies of Orthoherpesviridae, plays diverse and significant roles in viral replication, host–virus interactions and pathogenesis. Understanding the molecular mechanisms and interactions of UL24 proteins is key to unraveling the complex interplay between herpesviruses and their hosts. This review provides a comparative and comprehensive overview of current knowledge on UL24 family members, including their conservation, expression patterns, cellular localization, and functional roles upon their expression and during viral infection, highlighting their significance in herpesvirus biology and their potential functions. Full article
(This article belongs to the Special Issue The Evolution, Genetics and Pathogenesis of Viruses)
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Other

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6 pages, 574 KiB  
Brief Report
The Recurring Loss of ORF8 Secretion in Dominant SARS-CoV-2 Variants
by Joy-Yan Lam and Kin-Hang Kok
Int. J. Mol. Sci. 2025, 26(12), 5778; https://doi.org/10.3390/ijms26125778 - 16 Jun 2025
Viewed by 269
Abstract
The SARS-CoV-2 ORF8 protein is a unique accessory viral protein among human coronaviruses, characterized by recurrent deletions and mutations with functional consequences. In this short report, we demonstrate that several dominant SARS-CoV-2 strains, despite encoding ORF8, fail to secrete the protein, revealing a [...] Read more.
The SARS-CoV-2 ORF8 protein is a unique accessory viral protein among human coronaviruses, characterized by recurrent deletions and mutations with functional consequences. In this short report, we demonstrate that several dominant SARS-CoV-2 strains, despite encoding ORF8, fail to secrete the protein, revealing a recurring pattern of ORF8 functional impairment that cannot be detected by sequence analysis alone. In agreement with other studies, several high-frequency mutations were identified using the Nextstrain/augur pipeline, including G8Stop, Q27Stop, D119-/F120- double deletions, and nucleotide substitution C27889U, which occurred in XBB.1.5, Alpha, Delta, and BA.5.2 variants, respectively. Notably, the D119-/F120- deletions and C27889U substitution do not introduce premature stop codons, yet ORF8 secretion was lost in Delta and BA.5.2 virus-infected cultures. This indicates that the extracellular ORF8 function is impaired in these variants, resulting in ORF8 deficiency. Our findings highlight that the impairment of ORF8 secretion arises not only from premature stop codons but also from other mutations. Therefore, the functional validation of ORF8 secretion and activity is essential following sequence analysis to accurately assess ORF8’s role in SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue The Evolution, Genetics and Pathogenesis of Viruses)
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