Viruses

19 pages, 1564 KiB

Open AccessArticle

Single Amino Acid Residue W33 of tva Receptor Is Critical for Viral Entry and High-Affinity Binding of Avian Leukosis Virus Subgroup K

by Eliška Gáliková, David Přikryl, Salomé Prost, Dana Kučerová, Kateřina Trejbalová and Jiří Hejnar

Viruses 2025, 17(5), 709; https://doi.org/10.3390/v17050709 - 15 May 2025

Abstract

Avian leukosis virus (ALV), the prototypical alpharetrovirus, causes tumorigenesis, immunosuppression, and wasting disease in poultry. The ALV genus is classified into ten subgroups, which differ in their host range, cell tropism, and receptor usage. The subgroups A, B, K, and J cause significant [...] Read more.

Avian leukosis virus (ALV), the prototypical alpharetrovirus, causes tumorigenesis, immunosuppression, and wasting disease in poultry. The ALV genus is classified into ten subgroups, which differ in their host range, cell tropism, and receptor usage. The subgroups A, B, K, and J cause significant economic losses worldwide. The most recently discovered subgroup, ALV-K, which is now widespread in China, has been shown to use the tva cell receptor and share it with ALV-A. However, the specific amino acid residues crucial for ALV-K host cell entry remain unknown. Using precise tva expression and chimeric tva receptors, we further elucidated the significance of the cysteine-rich domain in mediating interactions with both ALV-A and ALV-K. Through a comprehensive analysis of mutated tva receptor variants, we pinpointed tryptophan at position 33 (W33) as a pivotal amino acid residue essential for ALV-K virus binding and entry. Of note is the finding that the substitution of W33 induced resistance to ALV-K while preserving sensitivity to ALV-A. This study not only represents an advance in the understanding of the specificity of the tva receptor for ALV-K, but also offers a biotechnological strategy for the prevention of ALV-K infections in poultry. Full article

(This article belongs to the Section Animal Viruses)

25 pages, 3117 KiB

Open AccessArticle

Postnatal Epigenetic Alterations in Calves Persistently Infected with Bovine Viral Diarrhea Virus

by Jessica N. Kincade, Dilyara A. Murtazina, Hanah M. Georges, Carolina L. Gonzalez-Berrios, Jeanette V. Bishop, Terry E. Engle, Marcela Henao-Tamayo, Jordan M. Eder, Erin M. McDonald, Darcy M. Deines, Brie M. Wright, Hana Van Campen and Thomas R. Hansen

Viruses 2025, 17(5), 708; https://doi.org/10.3390/v17050708 - 15 May 2025

Abstract

Bovine viral diarrhea virus (BVDV) is a globally prevalent pathogen causing severe detriment to the cattle industry. Vertical infection occurring before the development of the fetal adaptive immune response, before 125 days of gestation, results in an immunotolerant, persistently infected (PI) calf. It [...] Read more.

Bovine viral diarrhea virus (BVDV) is a globally prevalent pathogen causing severe detriment to the cattle industry. Vertical infection occurring before the development of the fetal adaptive immune response, before 125 days of gestation, results in an immunotolerant, persistently infected (PI) calf. It was hypothesized that epigenetic alterations observed in the splenic tissue of PI fetuses at gestational day 245 would persist into the postnatal period. White blood cell DNA from five PI and five control heifers at 4 months of age was subjected to reduced representation bisulfite sequencing and interpreted within the context of complete blood count and flow cytometry data herein. Analysis revealed 8367 differentially methylated sites contained within genes associated with the immune and cardiac system, as well as hematopoiesis. Differences observed in the complete blood counts of PI heifers include increased monocytes, microcytic anemia, and elevated platelets with decreased mean platelet volume. Flow cytometry revealed increased classical monocytes, B cells, and CD4⁺/CD8B⁺ and CD25⁺/CD127⁻ T cells, as well as decreased γδ⁺, CD4⁺, and CD4⁻/CD8B⁻ T cells. Investigation of the PI methylome provides a new perspective on the mechanisms of pathologies and provides potential biomarkers for the rapid identification of PI cattle. Full article

(This article belongs to the Special Issue Bovine Viral Diarrhea Viruses and Other Pestiviruses)

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18 pages, 5844 KiB

Open AccessArticle

Construction of Minigenome Replicon of Nipah Virus and Investigation of Biological Activity

by Fan Wang, Ruyi Chen, Jiayi Zhong, Anqi Zhou, Ran Peng, Bao Xue, Yuan Zhou, Jielin Tang, Xinwen Chen and Qi Yang

Viruses 2025, 17(5), 707; https://doi.org/10.3390/v17050707 - 15 May 2025

Abstract

Nipah virus (NiV), a highly lethal zoonotic pathogen causing encephalitis and respiratory diseases with mortality rates up to 40–70%, faces research limitations due to its strict biosafety level 4 (BSL-4) containment requirements, hindering antiviral development. To address this, we generated two NiV minigenome [...] Read more.

Nipah virus (NiV), a highly lethal zoonotic pathogen causing encephalitis and respiratory diseases with mortality rates up to 40–70%, faces research limitations due to its strict biosafety level 4 (BSL-4) containment requirements, hindering antiviral development. To address this, we generated two NiV minigenome replicons (Fluc- and EGFP-based) expressed via helper plasmids encoding viral N, P, and L proteins, enabling replication studies under BSL-2 conditions. The minigenome replicon recapitulated the cytoplasmic inclusion body (IB) formation observed in live NiV infections. We further demonstrated that IB assembly is driven by liquid–liquid phase separation (LLPS), with biochemical analyses identifying the C-terminal N core domain of the N protein, as well as N₀ and XD domains and the intrinsically disordered region (IDR) of the P protein, as essential structural determinants for LLPS-mediated IB biogenesis. The targeted siRNA silencing of the 5′ and 3′ untranslated regions (UTRs) significantly reduced replicon-derived mRNA levels, validating the regulatory roles of these regions. Importantly, the minigenome replicon demonstrated sensitivity to type I/II/III interferons and antivirals (remdesivir, azvudine, molnupiravir), establishing its utility for drug screening. This study provides a safe and efficient platform for investigating NiV replication mechanisms and accelerating therapeutic development, circumventing the constraints of BSL-4 facilities while preserving key virological features. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 4318 KiB

Open AccessBrief Report

Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal Infection

by Jonathan D. Joyce, Greyson A. Moore, Christopher K. Thompson and Andrea S. Bertke

Viruses 2025, 17(5), 706; https://doi.org/10.3390/v17050706 - 15 May 2025

Abstract

Neurological symptoms involving the central nervous system (CNS) and peripheral nervous system (PNS) are common complications of acute COVID-19 as well as post-COVID conditions. Most research into these neurological sequalae focuses on the CNS, disregarding the PNS. Guinea pigs were previously shown to [...] Read more.

Neurological symptoms involving the central nervous system (CNS) and peripheral nervous system (PNS) are common complications of acute COVID-19 as well as post-COVID conditions. Most research into these neurological sequalae focuses on the CNS, disregarding the PNS. Guinea pigs were previously shown to be useful models of disease during the SARS-CoV-1 epidemic. However, their suitability for studying SARS-CoV-2 has not been experimentally demonstrated. To assess the suitability of guinea pigs as models for SARS-CoV-2 infection and the impact of SARS-CoV-2 infection on the PNS, and to determine routes of CNS invasion through the PNS, we intranasally infected wild-type Dunkin-Hartley guinea pigs with ancestral SARS-CoV-2 USA-WA1/2020. We assessed PNS sensory neurons (trigeminal ganglia, dorsal root ganglia), autonomic neurons (superior cervical ganglia), brain regions (olfactory bulb, brainstem, cerebellum, cortex, hippocampus), lungs, and blood for viral RNA (RT-qPCR), protein (immunostaining), and infectious virus (plaque assay) at three- and six-days post infection. We show that guinea pigs, which have previously been used as a model of SARS-CoV-1 pulmonary disease, are not susceptible to intranasal infection with ancestral SARS-CoV-2, and are not useful models in assessing neurological impacts of infection with SARS-CoV-2 isolates from the early pandemic. Full article

(This article belongs to the Section Coronaviruses)

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14 pages, 686 KiB

Open AccessReview

Emerging Prognostic and Predictive Biomarkers for Human Cytomegalovirus Infection During Pregnancy: Unmet Needs and Future Perspectives

by Salvatore Rotundo, Maria Teresa Tassone, Rosaria Lionello, Paolo Fusco, Francesca Serapide and Alessandro Russo

Viruses 2025, 17(5), 705; https://doi.org/10.3390/v17050705 - 14 May 2025

Abstract

Human cytomegalovirus (HCMV) infection during pregnancy is a leading cause of congenital infections worldwide, posing significant risks to fetal health. Despite advances in prenatal care, managing HCMV infection remains challenging. Early detection, accurate risk assessment, and timely intervention are critical to mitigating the [...] Read more.

Human cytomegalovirus (HCMV) infection during pregnancy is a leading cause of congenital infections worldwide, posing significant risks to fetal health. Despite advances in prenatal care, managing HCMV infection remains challenging. Early detection, accurate risk assessment, and timely intervention are critical to mitigating the adverse outcomes associated with congenital HCMV (cHCMV), such as neurodevelopmental delays and hearing loss. However, the current landscape of biomarkers for HCMV infection in pregnancy is marked by several unmet needs. These gaps in biomarker development and application limit our ability to predict fetal transmission, assess the risk of fetal damage, and prognosticate long-term outcomes. Addressing these challenges through the identification and validation of novel biomarkers could revolutionize the management of HCMV in pregnancy, leading to improved outcomes for both mothers and their children. This review examines the critical unmet needs regarding HCMV biomarkers during pregnancy, emphasizing the priority areas for further research and innovation. Full article

(This article belongs to the Special Issue Molecular Biomarkers for Viral Infection)

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20 pages, 762 KiB

Open AccessArticle

Perinatal Mother-to-Child Chikungunya Virus Infection: Screening of Cognitive and Learning Difficulties in a Follow-Up Study of the Chimere Cohort on Reunion Island

by Raphaëlle Sarton, Magali Carbonnier, Stéphanie Robin, Duksha Ramful, Sylvain Sampériz, Pascale Gauthier, Marc Bintner, Brahim Boumahni and Patrick Gérardin

Viruses 2025, 17(5), 704; https://doi.org/10.3390/v17050704 - 14 May 2025

Abstract

In this cohort study, we evaluated the cognitive and learning difficulties of school-age children perinatally infected with Chikungunya virus (CHIKV) on Reunion Island using the Evaluation of Cognitive Functions and Learning in Children (EDA) battery screening test compared to the healthy children cohort [...] Read more.

In this cohort study, we evaluated the cognitive and learning difficulties of school-age children perinatally infected with Chikungunya virus (CHIKV) on Reunion Island using the Evaluation of Cognitive Functions and Learning in Children (EDA) battery screening test compared to the healthy children cohort used for EDA development. Of the 19 infected children, 11 (57.9%) exhibited subnormal or abnormal scores, of whom 3 were classified as high risk, and 8 were classified as at risk for cognitive and learning difficulties. Children who had encephalopathy were at higher risk for displaying at least one difficulty than non-encephalopathic children (relative risk 2.13; 95% CI 1.05–4.33). The difficulties observed affected verbal functions, non-verbal functions, and learning abilities, such as phonology, lexical evocation and comprehension, graphism, selective visual attention, planning, visual–spatial reasoning, dictation and mathematics, as well as core executive functions, such as inhibitory control, shifting, and working memory. Neurocognitive dysfunctions could be linked to severe brain damage, as evidenced by severe white matter reduction mainly in the frontal lobes and corpus callosum and potentially in all functional networks involved in difficulties. These results should motivate further investigation of intellectual and adaptive functioning to diagnose intellectual deficiency and severe maladaptive behaviour in children perinatally infected with Chikungunya virus. Full article

(This article belongs to the Special Issue Long-Term Developmental Outcomes of Congenital Virus Infections)

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18 pages, 2835 KiB

Open AccessArticle

Respiratory Syncytial Virus Elicits Glycolytic Metabolism in Pediatric Upper and Lower Airways

by Armando S. Flores-Torres, Svetlana Rezinciuc, Lavanya Bezavada, Barry L. Shulkin, Stephania A. Cormier and Heather S. Smallwood

Viruses 2025, 17(5), 703; https://doi.org/10.3390/v17050703 - 14 May 2025

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral infection in infants and causes around 60,000 in-hospital deaths annually. Emerging evidence suggests that RSV induces metabolic changes in host cells to support viral replication, presenting a potential target for [...] Read more.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract viral infection in infants and causes around 60,000 in-hospital deaths annually. Emerging evidence suggests that RSV induces metabolic changes in host cells to support viral replication, presenting a potential target for therapeutic intervention. To investigate RSV-driven metabolic changes in situ, we combined positron emission tomography (PET), live-cell bioenergetics, and metabolomic profiling in the upper and lower airways of children. PET imaging revealed persistent, hyper-glycolytic regions in the lungs of RSV-infected children. Bioenergetic analysis of freshly collected nasopharyngeal aspirates from infants showed live upper respiratory cells (URCs) infected with RSV in situ exhibited significantly higher levels of glycolysis, glycolytic capacity, glycolytic reserves, and mitochondrial respiration than uninfected controls. Metabolomic analysis of nasopharyngeal fluids from these patients revealed distinct metabolic signatures, including increased citrate and malate, and decreases in taurine. In vitro infection of pediatric nasopharynx tissue-derived multicellular epithelial cultures (TEpiCs) and bronchial epithelial cells further confirmed RSV-induced increases in glycolysis. Together, these findings demonstrate that RSV infection induces hypermetabolism in both upper and lower primary airways in situ, supporting the potential of host-targeted metabolic interventions as a therapeutic strategy—particularly in vulnerable populations such as infants for whom vaccines are not currently available. Full article

(This article belongs to the Section General Virology)

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14 pages, 596 KiB

Open AccessReview

Thermal Inactivation of Hepatitis E Virus: A Narrative Review

by Tatsuo Kanda and Hiroaki Okamoto

Viruses 2025, 17(5), 702; https://doi.org/10.3390/v17050702 - 14 May 2025

Abstract

Hepatitis E virus (HEV) infection is an emerging infectious disease. HEV-1 and HEV-2 infect humans through contaminated water and foods, mainly in developing countries. HEV-3 and HEV-4 also infect humans through contaminated food and are thought to be zoonotic infections occurring in both [...] Read more.

Hepatitis E virus (HEV) infection is an emerging infectious disease. HEV-1 and HEV-2 infect humans through contaminated water and foods, mainly in developing countries. HEV-3 and HEV-4 also infect humans through contaminated food and are thought to be zoonotic infections occurring in both developing and developed countries. A vaccine for hepatitis E is licensed in only limited countries. The inactivation of infectious HEV is very important to ensure the safety of drinking water and foods. HEV-3 and HEV-4 RNA have been detected in some pig liver products, and it is possible that these foods may represent an infectious source of HEV. In this article, previous publications on the heat inactivation and heat stability of HEV are collected, and we discuss the present assessment of the heat inactivation of HEV. The thermal stability of HEV infection in cell culture systems and pig bioassays has been demonstrated, while the efficacy of the method of thermal inactivation using plasma products has not yet been established. Here, we propose that the treatment of HEV-contaminated foods at 95 °C for 10 min is one of the safest options for the inactivation of HEV. Full article

(This article belongs to the Section Animal Viruses)

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23 pages, 3118 KiB

Open AccessArticle

Treatment of E. coli Infections with T4-Related Bacteriophages Belonging to Class Caudoviricetes: Selecting Phage on the Basis of Their Generalized Transduction Capability

by Alexandra N. Nikulina, Nikita A. Nikulin, Natalia E. Suzina and Andrei A. Zimin

Viruses 2025, 17(5), 701; https://doi.org/10.3390/v17050701 - 14 May 2025

Abstract

The problem of the multidrug resistance of pathogenic bacteria is a serious concern, one which only becomes more pressing with every year that passes, motivating scientists to look for new therapeutic agents. In this situation, phage therapy, i.e., the use of phages to [...] Read more.

The problem of the multidrug resistance of pathogenic bacteria is a serious concern, one which only becomes more pressing with every year that passes, motivating scientists to look for new therapeutic agents. In this situation, phage therapy, i.e., the use of phages to combat bacterial infections, is back in the spotlight of research interest. Bacterial viruses are highly strain-specific towards their hosts, which makes them particularly valuable for targeting pathogenic variants amidst non-pathogenic microflora, represented by such commensals of animals and humans as E. coli, S. aureus, etc. However, selecting phages for the treatment of bacterial infections is a complex task. The prospective candidates should meet a number of criteria; in particular, the selected phage must not contain potentially dangerous genes (e.g., antibiotic resistance genes, genes of toxins and virulence factors etc.)—or be capable of transferring them from their hosts. This work introduces a new approach to selecting T4-related coliphages; it allows one to identify strains which may be safer in terms of involvement in the horizontal gene transfer. The approach is based on the search for genes that reduce the frequency of genetic transduction. Full article

(This article belongs to the Section Bacterial Viruses)

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23 pages, 2899 KiB

Open AccessReview

A Systematic Study of Bovine Viral Diarrhoea Virus Co-Infection with Other Pathogens

by Zhiwei Hou, Jiahui Wang, Bin Tan and Shuqin Zhang

Viruses 2025, 17(5), 700; https://doi.org/10.3390/v17050700 - 14 May 2025

Abstract

Bovine viral diarrhoea virus (BVDV) is the causative agent of bovine viral diarrhoea/mucocutaneous disease (BVD-MD). Its associated co-infections pose a threat to the cattle industry, which is becoming a key breakthrough in the global system of prevention in the cattle industry. In recent [...] Read more.

Bovine viral diarrhoea virus (BVDV) is the causative agent of bovine viral diarrhoea/mucocutaneous disease (BVD-MD). Its associated co-infections pose a threat to the cattle industry, which is becoming a key breakthrough in the global system of prevention in the cattle industry. In recent years, cases of co-infection have occurred and been reported from time to time, and this situation not only poses certain difficulties in controlling the outbreak and in treatment in the farming industry, but also poses considerable challenges in detection and diagnosis. In this review, by systematically integrating studies on BVDV co-infection, we firstly compared and analysed the characteristics of BVDV co-infection with viruses, bacteria and other pathogens in in vivo/in vitro models in terms of synergism, host immune response and epidemiological transmission. Then we systematically constructed a BVDV Co-infection Impact Map, which demonstrates a paradigm of pathogen–host–immune interactions in the transmission of BVDV and provides a theoretical framework for breaking through the current precision diagnostic strategies and showcasing the effectiveness of integrated prevention and control. Full article

(This article belongs to the Special Issue Bovine Viral Diarrhea Viruses and Other Pestiviruses)

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8 pages, 776 KiB

Open AccessCase Report

Emergence of Bictegravir Resistance in a Treatment-Experienced PWH on Functional Monotherapy and Rapid Replacement by an Ancient Wild-Type Strain Following Transient Treatment Interruption

by Pietro B. Faré, Gabriela Ziltener, Judith Bergadà Pijuan, Irene A. Abela, Britta L. Hirsch, Michael Huber, Johannes Nemeth and Huldrych F. Günthard

Viruses 2025, 17(5), 699; https://doi.org/10.3390/v17050699 - 13 May 2025

Abstract

A treatment-experienced, highly adherent person living with HIV for over 25 years developed resistance mutations against all four major ART classes, including bictegravir (BIC). This led to viral failure on a quadruple regimen including BIC and doravirine (DOR). Resistance emergence was associated with [...] Read more.

A treatment-experienced, highly adherent person living with HIV for over 25 years developed resistance mutations against all four major ART classes, including bictegravir (BIC). This led to viral failure on a quadruple regimen including BIC and doravirine (DOR). Resistance emergence was associated with M184V, thymidine analog mutations (TAMs), NNRTI mutations (108I, 234I, 318F), and INSTI mutations (T97A, G140S, Q148H, G149A), likely driven by suboptimal BIC levels due to divalent cation interactions. During a two-month ART interruption, the resistant virus was rapidly replaced by an ancient wild-type strain. Despite resistance to all four ART classes, a genotype-adapted salvage regimen, including fostemsavir, achieved viral suppression within seven months. Full article

(This article belongs to the Special Issue Pharmacology of Antiviral Drugs, 2nd Edition)

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15 pages, 1084 KiB

Open AccessArticle

Surveillance and Molecular Characterization of Marek’s Disease Virus (MDV) Strains Circulating in Tanzania

by Augustino Alfred Chengula, Herbertha Mpete and Ramadhani Juma Makasali

Viruses 2025, 17(5), 698; https://doi.org/10.3390/v17050698 - 13 May 2025

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Abstract

Marek’s disease (MD) is a highly contagious and oncogenic viral disease of poultry, causing significant economic losses due to mortality and reduced performance. The rapid evolution of Marek’s disease virus (MDV) has been reported in poultry farms, often overcoming vaccination and leading to [...] Read more.

Marek’s disease (MD) is a highly contagious and oncogenic viral disease of poultry, causing significant economic losses due to mortality and reduced performance. The rapid evolution of Marek’s disease virus (MDV) has been reported in poultry farms, often overcoming vaccination and leading to disease outbreaks. This study aimed to detect and molecularly characterize circulating MDV strains in Tanzania, with a focus on their genetic relationship with the vaccine strains currently in use (HVT and CVI988). Samples were collected from six livestock representative zones in Tanzania (Central, Eastern, Southern, Southern Highlands, Lake, and Northern Zone) and analyzed using polymerase chain reaction (PCR) and sequencing of key oncogenic genes (meq, pp38, and vIL-8). Phylogenetic analysis was conducted using MEGA 12 software to determine the genetic relationships between Tanzanian isolates and MDV strains from Africa and other continents. The results confirm the widespread circulation of MDV in Tanzania, with an overall prevalence of 18.08% across all surveyed zones. Molecular characterization of the meq, pp38, and vIL-8 genes revealed high sequence similarity with previously reported MDV strains from Egypt, Nigeria, Israel, and China, with clustering observed in the phylogenetic analysis. Notably, Tanzanian MDV strains exhibited amino acid substitutions associated with increased virulence, particularly in the meq gene, which plays a crucial role in MDV-induced tumorigenesis. These findings suggest that MDV strains in Tanzania have undergone genetic changes that could potentially affect vaccine efficacy. Therefore, this study provides valuable information for vaccine manufacturers, poultry farmers, and policymakers in Tanzania, enabling informed decisions when selecting vaccines for MD control. Full article

(This article belongs to the Special Issue Marek's Disease Virus)

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22 pages, 6762 KiB

Open AccessArticle

A Novel Antiviral Therapeutic Platform: Anchoring IFN-β to the Surface of Infectious Virions Equips Interferon-Evasive Virions with Potent Antiviral Activity

by Hoda H. Jabbour, Alexander G. Bastian, Kayla B. DeOca and Mark D. Mannie

Viruses 2025, 17(5), 697; https://doi.org/10.3390/v17050697 - 13 May 2025

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Abstract

The COVID-19 pandemic highlighted the need for new therapeutic strategies to counter emerging pathogenic viruses. Herein, we introduce a novel fusion protein platform that enables antiviral targeting of distinct viral species based on host receptor specificity. Proof-of-concept studies focused on the human coronavirus [...] Read more.

The COVID-19 pandemic highlighted the need for new therapeutic strategies to counter emerging pathogenic viruses. Herein, we introduce a novel fusion protein platform that enables antiviral targeting of distinct viral species based on host receptor specificity. Proof-of-concept studies focused on the human coronavirus NL63, which shares specificity for the ACE2 host receptor with the pandemic SARS-CoV and SARS-CoV-2 species. This antiviral fusion protein combines IFN-β with the soluble extracellular domain of ACE2 (IFNβ-ACE2). Both domains retained predicted bioactivities in that the IFN-β domain exhibited potent antiproliferative activity and the ACE2 domain exhibited full binding to the transmembrane SARS-CoV-2 Spike protein. In virus-washed (virus-targeted) and non-washed in vitro infection systems, we showed that the pool of IFNβ-ACE2 targeted to the virion surface had superior antiviral activity against NL63 compared to soluble ACE2, IFN-β, or the unlinked combination of ACE2 and IFN-β. The pool of IFNβ-ACE2 on the virion surface exhibited robust antiviral efficacy based on the preemptive targeting of antiviral IFN-β activity to the proximal site of viral infection. In conclusion, virus-targeted IFN-β places interferon optimally and antecedent to viral infection to constitute a new antiviral strategy. Full article

(This article belongs to the Special Issue Innovative Drug Discovery for Emerging Viral Diseases)

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16 pages, 3159 KiB

Open AccessArticle

Genomic Diversity of Tomato Brown Rugose Fruit Virus in Canadian Greenhouse Production Systems

by Gregory C. Fougere, Dong Xu, Jonathan R. Gaiero, Cara McCreary, Geneviève Marchand, Charles Despres, Aiming Wang, Mamadou Lamine Fall and Jonathan S. Griffiths

Viruses 2025, 17(5), 696; https://doi.org/10.3390/v17050696 - 12 May 2025

Viewed by 162

Abstract

Tomato brown rugose fruit virus (ToBRFV) is a recently emerged viral pathogen in the Tobamovirus genus first observed in 2014 in the Middle East that has since spread worldwide, causing significant losses in greenhouse tomato production. ToBRFV is easily mechanically transmitted and can [...] Read more.

Tomato brown rugose fruit virus (ToBRFV) is a recently emerged viral pathogen in the Tobamovirus genus first observed in 2014 in the Middle East that has since spread worldwide, causing significant losses in greenhouse tomato production. ToBRFV is easily mechanically transmitted and can escape the durable Tm-2² resistance gene, facilitating its global spread. Seed companies have identified novel sources of resistance and introduced these resistance traits into commercial cultivars. The identity, number, and mechanisms of these putative novel resistance genes are largely unknown but could be exerting selective pressures on ToBRFV. Here, we report 15 new ToBRFV genomic sequences from Canadian greenhouse production systems in susceptible and novel resistant or tolerant cultivars collected since 2023. We combined these sequences with five other Canadian ToBRFV genomes previously deposited in Genbank and a further five consensus sequences derived from metagenomic-based wastewater monitoring sequence data and conducted phylogenetic analysis. Most Canadian sequences grouped together when compared with 332 publicly available international sequences, but several isolates appeared distantly related, suggesting multiple introductions to Canadian production systems. High sequence identity between samples suggest movement of ToBRFV between independent greenhouses, highlighting areas where biosecurity can be improved. Several novel non-synonymous polymorphisms identified in the p126 and movement protein (MP) open reading frames (ORFs) were unique to Canadian sequences and associated with infection of novel resistant tomato cultivars. Many polymorphisms in the p126 ORF are located in a region of the protein associated with Tm-1 resistance-breaking isolates of tomato mosaic virus and ToBRFV, but have not been previously reported. Four novel polymorphisms in MP were also identified and do not appear to be associated with sites previously identified as interacting with Tm-2² and could be related to other unknown resistance genes. Together, these results confirm the difficulties in preventing the transmission of ToBRFV, identify putative adaptations to novel and existing resistance genes, and emphasize the urgent need for the cloning and characterization of these new sources of resistance to ToBRFV. Full article

(This article belongs to the Special Issue Emerging and Reemerging Plant Viruses in a Changing World)

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15 pages, 6831 KiB

Open AccessArticle

Attenuation of a Virulent Porcine Deltacoronavirus Strain DHeB1 via Serial Passage in LLC-PK1 Cells

by Yuhan Zhang, Kang Liu, Longfei Chen, Meng Yuan, Hongyu Lu, Shaobo Xiao and Liurong Fang

Viruses 2025, 17(5), 695; https://doi.org/10.3390/v17050695 - 12 May 2025

Viewed by 148

Abstract

Porcine deltacoronavirus (PDCoV) is a newly discovered enteropathogenic coronavirus primarily responsible for diarrhea and mortality in piglets, with the potential to infect humans, thereby posing a significant threat to both human health and the global pig industry. Currently, there is no commercially available [...] Read more.

Porcine deltacoronavirus (PDCoV) is a newly discovered enteropathogenic coronavirus primarily responsible for diarrhea and mortality in piglets, with the potential to infect humans, thereby posing a significant threat to both human health and the global pig industry. Currently, there is no commercially available live-attenuated vaccine for PDCoV. In this study, an isolated virulent PDCoV strain, DHeB1, was continuously passaged in LLC-PK1 cells for up to 110 passages. The virus growth kinetics in cell culture and complete genome sequences of various passages (F11, F40, F70, F90, and F110) were determined. The results indicated significant increases in virus titers at passages F40 and F90. Sequence analysis revealed that only a few single-nucleotide mutations (some of which resulted in amino acid changes) and one nucleotide insertion were observed throughout successive passages. Notably, the eight and seven amino acid mutations that emerged in F40 and F70, respectively, remained stable in subsequent passages and were predominantly located in the S glycoprotein. The pathogenicity of F11, F40, F70, and F90 was assessed in 5-day-old piglets, revealing markedly reduced clinical symptoms, histopathological lesions, and intestinal PDCoV antigen distributions in piglets inoculated with F70 or F90. Importantly, F90 exhibited little to no virulence in piglets. The immunogenicity of F70, F90, and F110 was further evaluated in weaned piglets, with results indicating that the neutralizing antibody titers induced by F70 and F90 were comparable and significantly higher than those induced by F110. Collectively, these findings suggest that the PDCoV strain DHeB1 has been attenuated and can be used to develop a live-attenuated vaccine against PDCoV. Full article

(This article belongs to the Special Issue Porcine Viruses 2025)

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15 pages, 7777 KiB

Open AccessReview

Pathogenesis Induced by Influenza Virus Infection: Role of the Early Events of the Infection and the Innate Immune Response

by Alicia Helena Márquez-Bandala, Lourdes Gutierrez-Xicotencatl and Fernando Esquivel-Guadarrama

Viruses 2025, 17(5), 694; https://doi.org/10.3390/v17050694 - 12 May 2025

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Abstract

Infections by influenza A virus (IAV) are a significant cause of global mortality. The pathogenesis of the infection is usually studied in terms of direct viral-induced damage or the overreactive immune response that continues after the virus is cleared. However, factors such as [...] Read more.

Infections by influenza A virus (IAV) are a significant cause of global mortality. The pathogenesis of the infection is usually studied in terms of direct viral-induced damage or the overreactive immune response that continues after the virus is cleared. However, factors such as the initial infectious dose, the early response after infection in different cell types, and the presence of autoantibodies for relevant antiviral cytokines like type I IFNs seem to influence the course of the infection and lead to fatal outcomes. In this article, we address the current knowledge about the early events during influenza virus infection, which are important for their participation in influenza-derived pathogenesis. Full article

(This article belongs to the Special Issue Innate Immunity to Virus Infection 2nd Edition)

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17 pages, 1439 KiB

Open AccessReview

TAR RNA Mimicry of INI1 and Its Influence on Non-Integration Function of HIV-1 Integrase

by Ganjam V. Kalpana, Emilie Ernst and Swati Haldar

Viruses 2025, 17(5), 693; https://doi.org/10.3390/v17050693 - 11 May 2025

Viewed by 218

Abstract

HIV-1 integrase (IN), an essential viral protein that catalyzes integration, also influences non-integration functions such as particle production and morphogenesis. The mechanism by which non-integration functions are mediated is not completely understood. Several factors influence these non-integration functions, including the ability of IN [...] Read more.

HIV-1 integrase (IN), an essential viral protein that catalyzes integration, also influences non-integration functions such as particle production and morphogenesis. The mechanism by which non-integration functions are mediated is not completely understood. Several factors influence these non-integration functions, including the ability of IN to bind to viral RNA. INI1 is an integrase-binding host factor that influences HIV-1 replication at multiple stages, including particle production and particle morphogenesis. IN mutants defective for binding to INI1 are also defective for particle morphogenesis, similar to RNA-binding-defective IN mutants. Studies have indicated that the highly conserved Repeat (Rpt) 1, the IN-binding domain of INI1, structurally mimics TAR RNA, and that Rpt1 and TAR RNA compete for binding to IN. Based on the RNA mimicry, we propose that INI1 may function as a “place-holder” for viral RNA to facilitate proper ribonucleoprotein complex formation required during the assembly and particle morphogenesis of the HIV-1 virus. These studies suggest that drugs that target IN/INI1 interaction may lead to dual inhibition of both IN/INI1 and IN/RNA interactions to curb HIV-1 replication. Full article

(This article belongs to the Special Issue The 7th International Conference on Retroviral Integration)

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28 pages, 1434 KiB

Open AccessSystematic Review

Viral Threats to Australian Fish and Prawns: Economic Impacts and Biosecurity Solutions—A Systematic Review

by Md. Mizanur Rahaman, Bhavya Sharma, Saranika Talukder, Muhammad Jasim Uddin, Muhammad A. B. Siddik and Subir Sarker

Viruses 2025, 17(5), 692; https://doi.org/10.3390/v17050692 - 10 May 2025

Viewed by 164

Abstract

Viral diseases pose significant threats to aquaculture industries worldwide, including the Australian fish and prawn farming sectors, which contribute over AUD 1.6 billion annually to the national economy. The Australian aquaculture industry relies heavily on wild-caught broodstock for seedstock production, introducing substantial and [...] Read more.

Viral diseases pose significant threats to aquaculture industries worldwide, including the Australian fish and prawn farming sectors, which contribute over AUD 1.6 billion annually to the national economy. The Australian aquaculture industry relies heavily on wild-caught broodstock for seedstock production, introducing substantial and unprecedented biosecurity risks. This systematic review consolidates current knowledge on the viral pathogens affecting key Australian fish and prawn species, their economic impacts, and the biosecurity measures implemented for mitigation. Notably, viral outbreaks have led to losses exceeding AUD 100 million in some sectors, highlighting the urgent need for improved management. Existing biosecurity strategies, including surveillance systems, molecular diagnostics, and pathogen exclusion protocols, are critically assessed for their effectiveness. Emerging approaches such as genetic resistance breeding, advanced vaccination technologies, and integrated risk management frameworks are also explored. Key knowledge gaps, particularly in the context of emerging viral pathogens and their ecological interactions under changing environmental conditions, are identified as priority areas for future research. This review emphasises the necessity of adopting a multidisciplinary approach to enhance the resilience of Australian aquaculture, advocating for stronger biosecurity frameworks and innovative technologies to mitigate the escalating risks posed by viral diseases. Full article

(This article belongs to the Special Issue Aquatic Animal Viruses and Antiviral Immunity)

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26 pages, 1846 KiB

Open AccessReview

Receptor Binding for the Entry Mechanisms of SARS-CoV-2: Insights from the Original Strain and Emerging Variants

by Mohamed Mahdi, Irene Wanjiru Kiarie, János András Mótyán, Gyula Hoffka, Aya Shamal Al-Muffti, Attila Tóth and József Tőzsér

Viruses 2025, 17(5), 691; https://doi.org/10.3390/v17050691 - 10 May 2025

Viewed by 156

Abstract

Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved, giving rise to multiple variants that have significantly altered the trajectory of the COVID-19 pandemic. These variants have resulted in multiple waves of the pandemic, exhibiting characteristic [...] Read more.

Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continuously evolved, giving rise to multiple variants that have significantly altered the trajectory of the COVID-19 pandemic. These variants have resulted in multiple waves of the pandemic, exhibiting characteristic mutations in the spike (S) protein that may have affected receptor interaction, tissue tropism, and cell entry mechanisms. While the virus was shown to primarily utilize the angiotensin-converting enzyme 2 (ACE2) receptor and host proteases such as transmembrane serine protease 2 (TMPRSS2) for entry into host cells, alterations in the S protein have resulted in changes to receptor binding affinity and use of alternative receptors, potentially expanding the virus’s ability to infect different cell types or tissues, contributing to shifts in clinical presentation. These changes have been linked to variations in disease severity, the emergence of new clinical manifestations, and altered transmission dynamics. In this paper, we overview the evolving receptor utilization strategies of SARS-CoV-2, focusing on how mutations in the S protein may have influenced viral entry mechanisms and clinical outcomes across the ongoing pandemic waves. Full article

(This article belongs to the Special Issue Mechanism of Receptor Recognition in Coronavirus, 2nd Edition)

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8 pages, 365 KiB

Open AccessCommentary

The Need for the Optimization of HIV Antiretroviral Therapy in Kazakhstan

by Aidana Mustafa, Natalya Dzissyuk, Bauyrzhan Bayserkin, Dinara Begimbetova, Zhamilya Nugmanova and Syed Ali

Viruses 2025, 17(5), 690; https://doi.org/10.3390/v17050690 - 10 May 2025

Viewed by 163

Abstract

The number of people living with HIV in Kazakhstan increased from 11,000 to 35,000 between 2010 and 2021, with emerging antiretroviral therapy (ART) resistance posing a challenge to effective treatment. Unsafe injection practices among people who inject drugs (PWID), the stigma against men [...] Read more.

The number of people living with HIV in Kazakhstan increased from 11,000 to 35,000 between 2010 and 2021, with emerging antiretroviral therapy (ART) resistance posing a challenge to effective treatment. Unsafe injection practices among people who inject drugs (PWID), the stigma against men who have sex with men, sex work, drug possession, HIV transmission, HIV exposure, and the non-disclosure of HIV status create obstacles to effective prevention and care. Our recent studies with people living with HIV (PLWH) in Kazakhstan have revealed the prevalence of mutations in HIV that may confer resistance to certain ART components currently being administered in the country. Additionally, subtype A6- and CRF02_AG-infected PLWH displayed the occurrence of certain distinct subtype-specific DRMs. Subtype A6 exhibited a tendency for the DRMs A62V, G190S, K101E, D67N, and V77I, whereas CRF02_AG was more associated with S162A, K103N, and V179E. Both subtypes had a comparable frequency of the M184V mutation and displayed similar patterns in the distribution of Q174K. Based on our findings, we recommend that DRM screening and subtype diagnosis before the initiation of ART will improve treatment efficiency while preventing the emergence of further DRMs in Kazakhstan. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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11 pages, 2084 KiB

Open AccessReview

How HIV-1 Uses the Metabolite Inositol Hexakisphosphate to Build Its Capsid

by Leo C. James

Viruses 2025, 17(5), 689; https://doi.org/10.3390/v17050689 - 9 May 2025

Viewed by 165

Abstract

The HIV-1 capsid is one of virology’s most iconic structures, yet how it assembles has long remained elusive. Remarkably, the capsid is made from just a single protein, CA, which forms a lattice of ~250 hexamers and exactly 12 pentamers. Conical capsids form [...] Read more.

The HIV-1 capsid is one of virology’s most iconic structures, yet how it assembles has long remained elusive. Remarkably, the capsid is made from just a single protein, CA, which forms a lattice of ~250 hexamers and exactly 12 pentamers. Conical capsids form inside budded virions during maturation, but early efforts to reproduce this in vitro resulted instead in open-ended tubes with a purely hexameric lattice. The missing component in capsid assembly was finally identified as the metabolite inositol hexakisphosphate (IP6). Simply mixing soluble CA protein with IP6 is sufficient to drive the spontaneous assembly of conical capsids with a similar size and shape to those inside of infectious virions. Equally important, IP6 stabilises capsids once formed, increasing their stability from minutes to hours. Indeed, such is the dependence of HIV-1 on IP6 that the virus actively packages it into virions during production. These discoveries have stimulated work from multiple labs into the role and importance of IP6 in HIV-1 replication, and is the subject of this review. Full article

(This article belongs to the Special Issue 15-Year Anniversary of Viruses)

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14 pages, 1756 KiB

Open AccessArticle

Development of a Pentacistronic Ebola Virus Minigenome System

by Brady N. Zell, Vaille A. Swenson, Shao-Chia Lu, Lin Wang, Michael A. Barry, Hideki Ebihara and Satoko Yamaoka

Viruses 2025, 17(5), 688; https://doi.org/10.3390/v17050688 - 9 May 2025

Viewed by 224

Abstract

Ebola virus (EBOV) causes severe disease outbreaks in humans with high case fatality rates. EBOV requires adaptation to cause lethal disease in mice by acquiring single mutations in both the nucleoprotein (NP) and VP24 genes. As an attempt to model mouse-adapted EBOV (MA-EBOV), [...] Read more.

Ebola virus (EBOV) causes severe disease outbreaks in humans with high case fatality rates. EBOV requires adaptation to cause lethal disease in mice by acquiring single mutations in both the nucleoprotein (NP) and VP24 genes. As an attempt to model mouse-adapted EBOV (MA-EBOV), we engineered novel pentacistronic minigenomes (5xMG) containing a reporter gene, VP40, and glycoprotein genes as well as the NP and VP24 genes from either EBOV or MA-EBOV. The 5xMGs were constructed and optimized, and the produced transcription- and replication-competent virus-like particles (trVLPs) were demonstrated to infect several cell lines. Introduction of the mouse-adaptation mutations did not significantly impact the replication and transcription of the 5xMG or the relative infectivity of the trVLPs in vitro. This work demonstrates the development of the 5xMG system as a new versatile tool to study EBOV biology. Full article

(This article belongs to the Special Issue BSL4 Viruses: Understanding and Controlling Highly Infectious Pathogens)

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13 pages, 1232 KiB

Open AccessArticle

Investigation of β-Carboline Alkaloid Harmaline Against Cyvirus cyprinidallo3 Infection In Vitro and In Vivo

by Clement Manes, Kristen Larson, Shelby Matsuoka, Xisheng Wang, Ruth Milston-Clements and Ling Jin

Viruses 2025, 17(5), 687; https://doi.org/10.3390/v17050687 - 9 May 2025

Viewed by 197

Abstract

Cyvirus cyprinidallo3, also known as Cyprinid herpesvirus 3 (CyHV-3), is a common pathogen of koi and common carp (Cyprinus carpio). Infection of CyHV-3 can lead to high mortality in fry under 4 months of age. CyHV-3 can become latent in [...] Read more.

Cyvirus cyprinidallo3, also known as Cyprinid herpesvirus 3 (CyHV-3), is a common pathogen of koi and common carp (Cyprinus carpio). Infection of CyHV-3 can lead to high mortality in fry under 4 months of age. CyHV-3 can become latent in recovered fish, and latent CyHV-3 can reactivate under stress conditions and spread the virus. Reactivation of CyHV-3 can also lead to mortality and diseases in latently infected fish. No effective drugs are available to prevent CyHV-3 infection or reactivation from latency. There is a need for the discovery of anti-CyHV-3 drugs. Harmine (HAR) and harmaline (HAL) are β-carboline alkaloids found in the medicinal plant Peganum harmala with antiviral activities against many viruses, including HSV. Here, HAL was evaluated against CyHV-3 infection in vitro and in vivo, respectively. Immediately after a one-hour infection exposure of ~1000 FPU/plate or ~500 PFU/plate, cells treated with 5 µM HAL for 2 h can block nearly 50% or 90% plaque formation in vitro. Only around 50% inhibition was observed in cells treated with the common anti-herpesvirus drug acyclovir (ACV) at 10 or 20 µM for 2 h following 1 h post-infection of ~500 PFU/plate. Cells treated with 10 µM HAL for 30 min, 60 min, 2 h, and 6 h can reduce 60%, 65%, 85.5%, and 85% CyHV-3 replication in vitro, respectively. HAL at 20 µM is still effective against CyHV-3 DNA replication and virion production when the treatment started at 3 and 5 days post-infection for 1 or 2 h, respectively. HAL under 50 µM has little toxicity to cells treated for 24 h. Immersion treatment with 10 µM HAL for 3–4 h daily within the first 5 days post-infection can increase the survival of fry by 60%. In addition, IM injection of HAL at 20 µM can reduce the rate of CyHV-3 reactivation induced by heat stress in latently infected koi. This study demonstrated that HAL could potentially be used to prevent CyHV-3 infection or reactivation from latency. Full article

(This article belongs to the Section Animal Viruses)

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14 pages, 4177 KiB

Open AccessArticle

A Bioluminescent Imaging Mouse Model for Seasonal Influenza Virus Infection Based on a Pseudovirus System

by Yifei Wang, Mengyi Zhang, Yimeng An, Lanshu Li, Hao Wu, Ziqi Cheng, Ling Pan, Chaoying Yang, Weijin Huang, Yansheng Geng and Chenyan Zhao

Viruses 2025, 17(5), 686; https://doi.org/10.3390/v17050686 - 9 May 2025

Viewed by 143

Abstract

Influenza (flu) is a highly prevalent respiratory illness caused by influenza viruses, representing a significant global health burden due to its substantial morbidity and mortality rate. Vaccination remains the most effective strategy for influenza prevention, and well-characterized animal models of influenza infection serve [...] Read more.

Influenza (flu) is a highly prevalent respiratory illness caused by influenza viruses, representing a significant global health burden due to its substantial morbidity and mortality rate. Vaccination remains the most effective strategy for influenza prevention, and well-characterized animal models of influenza infection serve as essential tools for evaluating vaccine protective efficacy. However, animal models utilizing live influenza virus strains pose significant biosafety concerns, and many such strains are not readily available for research. To address these challenges, we established a novel visual mouse infection model using an HIV-based vector system. This model employs influenza pseudoviruses carrying a luciferase reporter gene, enabling real-time monitoring of viral load and in vivo tracking of viral distribution during infection. Using this infection model, we assessed the in vivo protective efficacy of an influenza vaccine and cross-validated the pseudovirus-based evaluation results against a live virus-infected mouse model. Our study thus establishes a safer and more convenient platform for evaluating influenza vaccine efficacy, including the assessment of broad-spectrum neutralization capacity. Full article

(This article belongs to the Section Animal Viruses)

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15 pages, 2079 KiB

Open AccessArticle

Genetic Characterization of Kazakhstan Isolates: Avian Influenza H9N2 Viruses Demonstrate Their Potential to Infect Mammals

by Barshagul Baikara, Kobey Karamendin, Yermukhammet Kassymbekov, Klara Daulbayeva, Temirlan Sabyrzhan, Sardor Nuralibekov, Yelizaveta Khan, Nurlan Sandybayev, Sasan Fereidouni and Aidyn Kydyrmanov

Viruses 2025, 17(5), 685; https://doi.org/10.3390/v17050685 - 8 May 2025

Viewed by 577

Abstract

Low pathogenic H9N2 avian influenza viruses have become widespread in wild birds and poultry worldwide, raising concerns about their potential to spark pandemics or their role in enhancing the virulence and infectivity of H5Nx viruses through genetic reassortment. Therefore, influenza monitoring studies, including [...] Read more.

Low pathogenic H9N2 avian influenza viruses have become widespread in wild birds and poultry worldwide, raising concerns about their potential to spark pandemics or their role in enhancing the virulence and infectivity of H5Nx viruses through genetic reassortment. Therefore, influenza monitoring studies, including those of H9N2 viruses, are crucial for understanding, evaluating, and mitigating the risks associated with avian infections, and have broader implications for global public health. Although H9N2 viruses are not considered enzootic in Kazakhstan, they have been repeatedly detected in wild waterfowls and domestic poultry. In this study, all eight gene segments of influenza A/H9N2 viruses isolated in various regions of Kazakhstan between 2014 and 2020 were sequenced and analyzed. Molecular characterization revealed the presence of genetic markers associated with mammalian infectivity and disease potential. Furthermore, their predicted receptor binding site sequences indicate their potential capacity to attach to human-type receptors. These findings highlight the importance of continued surveillance and molecular investigation to better understand the evolution and zoonotic potential of H9N2 viruses in Kazakhstan. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Evolution, and Transmission of Avian Influenza Viruses)

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17 pages, 2367 KiB

Open AccessArticle

Higher Rates of Viral Evolution in Chronic Hepatitis B Patients Linked to Predicted T Cell Epitopes

by Magnus Illum Dalegaard, Anni Winckelmann, Ulrik Fahnøe, Alexander P. Underwood, Anders Gorm Pedersen, Signe Bollerup, Jens Bukh and Nina Weis

Viruses 2025, 17(5), 684; https://doi.org/10.3390/v17050684 - 8 May 2025

Viewed by 403

Abstract

The impact of hepatitis B virus (HBV) diversity and evolution on disease progression is not well-understood. This study aims to compare intra-individual viral evolution in two groups of chronic hepatitis B (CHB) patients, using antiviral treatment initiation as a measure of lack of [...] Read more.

The impact of hepatitis B virus (HBV) diversity and evolution on disease progression is not well-understood. This study aims to compare intra-individual viral evolution in two groups of chronic hepatitis B (CHB) patients, using antiviral treatment initiation as a measure of lack of immunological control. From the Danish Database for Hepatitis B and C (DANHEP), 25 CHB patients were included; 14 with antiviral treatment initiation (TI group), and 11 without (NTI group). For each patient, three serial plasma samples taken before potential treatment initiation were selected. HBV DNA was amplified by PCR and analyzed by next-generation sequencing. HBV DNA and alanine transaminase were elevated in the TI group throughout the study period. Significantly higher substitution rates in the NTI group versus the TI group were found both within the viral population and at consensus level. Putative predicted CD8⁺ T cell epitopes contained significantly more substitutions in the NTI group. Genome-wide association analysis revealed several amino acid residues in the HBV genome associated with treatment initiation. This study shows that HBV has a higher rate of substitutions in CHB patients not requiring treatment. This could be linked to host immune pressure leading to disease control. Full article

(This article belongs to the Section Human Virology and Viral Diseases)

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1 pages, 140 KiB

Open AccessCorrection

Correction: López-Ferber et al. Baculovirus Genetic Diversity and Population Structure. Viruses 2025, 17, 142

by Miguel López-Ferber, Primitivo Caballero and Trevor Williams

Viruses 2025, 17(5), 683; https://doi.org/10.3390/v17050683 - 7 May 2025

Viewed by 101

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Insect Viruses and Pest Management, the Third Edition)

20 pages, 2012 KiB

Open AccessReview

Multidimensional Regulatory Mechanisms and Targeting Strategies of the eEF1 Family in RNA Virus Infection

by Xin Wang, Kaituo Liu, Xiaoquan Wang and Xiufan Liu

Viruses 2025, 17(5), 682; https://doi.org/10.3390/v17050682 - 7 May 2025

Viewed by 192

Abstract

The eukaryotic translation elongation factor 1 (eEF1) family exhibits critical roles in RNA viral infection beyond its canonical function in protein synthesis. This review analyzes the structural characteristics of eEF1A and the eEF1B complex, and their regulatory mechanisms during viral infection. eEF1A impacts [...] Read more.

The eukaryotic translation elongation factor 1 (eEF1) family exhibits critical roles in RNA viral infection beyond its canonical function in protein synthesis. This review analyzes the structural characteristics of eEF1A and the eEF1B complex, and their regulatory mechanisms during viral infection. eEF1A impacts viral replication by stabilizing viral RNA-dependent RNA polymerase (RdRp) complexes, modulating genomic RNA synthesis, and facilitating viral assembly through cytoskeletal regulation. eEF1B subunits contribute through enhancing viral mRNA translation, regulating nuclear transport of viral components, and mediating post-translational modifications. The high conservation of eEF1 proteins across species and their involvement in multiple stages of viral replication establish them as promising broad-spectrum antiviral targets. Current eEF1-targeting compounds like plitidepsin demonstrate efficacy against diverse viral families, though therapeutic development faces challenges in balancing antiviral activity with host toxicity. This review provides a theoretical foundation for developing novel antiviral strategies targeting host–virus interaction interfaces and offers insights into addressing emerging infectious diseases. Full article

(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)

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14 pages, 6054 KiB

Open AccessArticle

Virtual Screening and Molecular Dynamics Simulation Targeting the ATP Domain of African Swine Fever Virus Type II DNA Topoisomerase

by Rui Zhao, Lezi Hou, Weldu Tesfagaber, Linfei Song, Zhenjiang Zhang, Fang Li, Zhigao Bu and Dongming Zhao

Viruses 2025, 17(5), 681; https://doi.org/10.3390/v17050681 - 7 May 2025

Viewed by 159

Abstract

African Swine Fever Virus (ASFV) Topo II ATPase domain, resistant to conventional inhibitors (e.g., ICRF-187) due to M18/W19 steric clashes, was targeted via hierarchical virtual screening (Schrödinger) of the Chembridge library combined with MM/GBSA calculations. Five ligands (10012949, 40242484, 46712145, 15880207, and 33688815) [...] Read more.

African Swine Fever Virus (ASFV) Topo II ATPase domain, resistant to conventional inhibitors (e.g., ICRF-187) due to M18/W19 steric clashes, was targeted via hierarchical virtual screening (Schrödinger) of the Chembridge library combined with MM/GBSA calculations. Five ligands (10012949, 40242484, 46712145, 15880207, and 33688815) showed high affinity, with 46712145 adopting symmetrical π–π stacking, hydrogen bonds, and alkyl interactions to bypass steric hindrance. Molecular dynamics simulations (100 ns) revealed ligand-induced flexibility, evidenced by elevated RMSD/Rg values versus the free protein. DCCM analysis highlighted enhanced anti-correlated motions between GHKL motifs and sensor domains in chain B/C, suggesting stabilization of a non-catalytic conformation to inhibit ATP hydrolysis. Free energy landscape (FEL) analysis showed 46712145 occupying a broad, shallow energy basin, enabling conformational adaptability, contrasting the narrow deep well of the free protein. This study proposes a symmetric ligand design strategy and conformational capture mechanism to block ATPase activity. Compound 46712145 demonstrates stable binding and dynamic regulation, providing a novel lead scaffold for anti-ASFV drug development. These findings establish a structural framework for combating ASFV through targeted ATPase inhibition. Full article

(This article belongs to the Section Animal Viruses)

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18 pages, 2869 KiB

Open AccessHypothesis

A Model of Non-Homologous Recombination Mediated by HIV-1 Reverse Transcriptase Explaining Sequence Motif Duplications That Confer a Replication Fitness Advantage

by Arun Panchapakesan and Udaykumar Ranga

Viruses 2025, 17(5), 680; https://doi.org/10.3390/v17050680 - 7 May 2025

Viewed by 142

Abstract

The Reverse Transcriptase of the Human Immunodeficiency Virus (HIV) is distinguished by its high rate of homologous recombination. A less-studied consequence of this phenomenon is the increased occurrence of non-homologous recombination, which results in length polymorphism. While most of these genome-wide variations are [...] Read more.

The Reverse Transcriptase of the Human Immunodeficiency Virus (HIV) is distinguished by its high rate of homologous recombination. A less-studied consequence of this phenomenon is the increased occurrence of non-homologous recombination, which results in length polymorphism. While most of these genome-wide variations are sporadic, some provide a replication advantage to variant strains, such as those in the Long Terminal Repeat (LTR) and p6-Gag regions. By analyzing sequences from these two regions in the HIV-1 databases, we categorize all types of non-homologous recombination into four groups based on the presence or absence of two molecular features. Additionally, drawing on established models of homologous recombination, we propose a model that describes the process of sequence duplication. This model can also be applied to explain non-homologous recombination in different types of HIV and other viruses. Full article

(This article belongs to the Special Issue Regulation of HIV-1 Transcription and Latency, 2nd Edition)

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