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The Spleen Virome of Australia’s Endemic Platypus Is Dominated by Highly Diverse Papillomaviruses
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Marek’s Disease Virus (MDV) Meq Oncoprotein Plays Distinct Roles in Tumor Incidence, Distribution, and Size
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Fluorescent Clade IIb Lineage B.1 Mpox Viruses for Antiviral Screening
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Structural Analysis of Inhibitor Binding to Enterovirus-D68 3C Protease
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The Dissemination of Rift Valley Fever Virus to the Eye and Sensory Neurons of Zebrafish Larvae Is Stat1-Dependent
Journal Description
Viruses
Viruses
is a peer-reviewed, open access journal of virology, published monthly online by MDPI. The Spanish Society for Virology (SEV), Canadian Society for Virology (CSV), Italian Society for Virology (SIV-ISV), Australasian Virology Society (AVS) and others are affiliated with Viruses and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, PubAg, AGRIS, and other databases.
- Journal Rank: JCR - Q2 (Virology) / CiteScore - Q1 (Infectious Diseases)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.1 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journal: Zoonotic Diseases.
Impact Factor:
3.8 (2023);
5-Year Impact Factor:
4.0 (2023)
Latest Articles
The Individual and Combined Entomopathogenic Activity of a Spodoptera frugiperda Multiple Nucleopolyhedrovirus and a Type I Spodoptera frugiperda Granulovirus on S. frugiperda Larvae
Viruses 2025, 17(5), 674; https://doi.org/10.3390/v17050674 (registering DOI) - 5 May 2025
Abstract
The bioinsecticidal activity of several doses of a Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV-CH-32; LD10, LD50, and LD90) and a Type I Spodoptera frugiperda granulovirus (SfGV-CH13; LD50 and LD90), alone and in co-infection, was evaluated
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The bioinsecticidal activity of several doses of a Spodoptera frugiperda multiple nucleopolyhedrovirus (SfMNPV-CH-32; LD10, LD50, and LD90) and a Type I Spodoptera frugiperda granulovirus (SfGV-CH13; LD50 and LD90), alone and in co-infection, was evaluated on S. frugiperda larvae. In the co-infection assays, one virus was applied at 0 h, and then the second virus was supplied at different times (0, 12, and 24 h) in order to test the effect of the co-infection time on the insecticidal activity of the viruses. The symptoms observed in the co-infected larvae depended on the viral dose supplied at 0 h. The larvae treated with the highest dose (LD90) of SfMNPV-CH32 and co-infected with SfGV-CH13 at LD50 showed symptoms of nucleopolyhedrovirus infection at 14 days post-infection. The larvae initially infected with the highest dose of SfGV-CH13 (LD90) and subsequently co-infected with SfMNPV-CH32 (LD50 and LD10) showed infection symptoms characteristic of both viruses. The insecticidal activity of SfGV-CH13 and SfMNPV-CH32 alone or in combination depended on the viral doses and the time elapsed between the first and second inoculation. An antagonistic effect was observed for most of the treatments tested. A synergistic effect was observed only in treatment 10, where the larvae were first infected with SfMNPV-CH32 at a high dose (LD90) and inoculated 24 h later with SfGV-CH13 (LD50).
Full article
(This article belongs to the Special Issue Insect Viruses and Pest Management, the Third Edition)
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Open AccessCommunication
Return of the Biennial Circulation of Enterovirus D68 in Colorado Children in 2024 Following the Large 2022 Outbreak
by
Hai Nguyen-Tran, Molly Butler, Dennis Simmons, Samuel R. Dominguez and Kevin Messacar
Viruses 2025, 17(5), 673; https://doi.org/10.3390/v17050673 - 5 May 2025
Abstract
Enterovirus D68 (EV-D68) caused large biennial cyclical outbreaks of respiratory disease and cases of acute flaccid myelitis from 2014 to 2018 in the USA. An anticipated outbreak did not occur in 2020, likely due to non-pharmaceutical interventions targeting the COVID-19 pandemic. A large
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Enterovirus D68 (EV-D68) caused large biennial cyclical outbreaks of respiratory disease and cases of acute flaccid myelitis from 2014 to 2018 in the USA. An anticipated outbreak did not occur in 2020, likely due to non-pharmaceutical interventions targeting the COVID-19 pandemic. A large respiratory disease outbreak occurred again in 2022, but uncertainty remained regarding if circulation of EV-D68 would return to the pre-pandemic patterns. We conducted prospective active surveillance of clinical respiratory specimens from Colorado children for EV-D68 in 2023 and 2024. A subset of residual specimens positive for rhinovirus/enterovirus (RV/EV) were tested for EV-D68 via a validated in-house EV-D68 reverse transcription–PCR assay. During epi weeks 18–44 in 2023, 525 residual specimens positive for RV/EV all tested negative for EV-D68. In 2024, during epi weeks 18–44, 10 (1.8%) of the 546 RV/EV-positive specimens were EV-D68-positive. The EV-D68-positive cases were predominantly young children (median age 4.8 years) receiving treatment with asthma medications. Following the 2022 EV-D68 outbreak, an anticipated outbreak did not occur in 2023. While EV-D68 was detected in 2024, the number of cases was not as significant as in prior outbreak years. Continued surveillance for EV-D68 will be important to understand the future dynamics of EV-D68 circulation and prepare for future outbreaks.
Full article
(This article belongs to the Special Issue An Update on Enterovirus Research, 2nd Edition)
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Evaluating Population Normalization Methods Using Chemical Data for Wastewater-Based Epidemiology: Insights from a Site-Specific Case Study
by
Marco Verani, Ileana Federigi, Alessandra Angori, Alessandra Pagani, Francesca Marvulli, Claudia Valentini, Nebiyu Tariku Atomsa, Beatrice Conte and Annalaura Carducci
Viruses 2025, 17(5), 672; https://doi.org/10.3390/v17050672 - 4 May 2025
Abstract
Wastewater-based epidemiology (WBE) has been widely employed to track the spread of human pathogens; however, correlating wastewater data with clinical surveillance remains challenging due to population variability and environmental factors affecting wastewater composition. This study evaluated different SARS-CoV-2 normalization methods, comparing static population
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Wastewater-based epidemiology (WBE) has been widely employed to track the spread of human pathogens; however, correlating wastewater data with clinical surveillance remains challenging due to population variability and environmental factors affecting wastewater composition. This study evaluated different SARS-CoV-2 normalization methods, comparing static population estimates with dynamic normalization based on common physicochemical parameters: chemical oxygen demand (COD), biochemical oxygen demand (BOD5), and ammonia (NH4-N). Wastewater samples were collected from four urban wastewater treatment plants (WWTPs) in northwestern Tuscany (Italy) from February 2021 to March 2023. The correlations between normalized viral loads and clinical COVID-19 cases were highest for static normalization (ρ = 0.405), followed closely by dynamic normalization using COD and BOD5 (ρ = 0.378 each). Normalization based on NH4-N was less effective. These findings suggest that chemical parameters, particularly COD and BOD5, offer a valid alternative for viral normalization when population estimates or flow rate measurements are unavailable. These parameters provide a cost-effective and practical approach for improving WBE reliability, particularly in resource-limited settings. Our results reinforce the importance of normalization in WBE to enhance its representativeness and applicability for public health surveillance.
Full article
(This article belongs to the Section General Virology)
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KRT6A Restricts Influenza A Virus Replication by Inhibiting the Nuclear Import and Assembly of Viral Ribonucleoprotein Complex
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Yu Chang, Zhibo Shan, Wenjun Shi, Qibing Li, Yihan Wang, Bo Wang, Guangwen Wang, Hualan Chen, Li Jiang and Chengjun Li
Viruses 2025, 17(5), 671; https://doi.org/10.3390/v17050671 - 4 May 2025
Abstract
The transcription and replication of the genome of influenza A virus (IAV) take place in the nucleus of infected cells, which is catalyzed by the viral ribonucleoprotein (vRNP) complex. The nuclear import of the vRNP complex and its component proteins is essential for
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The transcription and replication of the genome of influenza A virus (IAV) take place in the nucleus of infected cells, which is catalyzed by the viral ribonucleoprotein (vRNP) complex. The nuclear import of the vRNP complex and its component proteins is essential for the efficient replication of IAV and is therefore prone to be targeted by host restriction factors. Herein, we found that host cellular protein keratin 6A (KRT6A) is a negative regulator of IAV replication because siRNA-mediated knockdown of KRT6A expression increased the growth titers of IAV, whereas exogenous overexpression of KRT6A reduced viral yields. The nuclear import of incoming vRNP complexes and newly synthesized nucleoprotein (NP) was significantly impaired when KRT6A was overexpressed. Further studies showed that KRT6A interacts with the four vRNP complex proteins—polymerase basic protein 1 (PB1), polymerase basic protein 2 (PB2), polymerase acidic protein (PA), and NP. Notably, the interaction between KRT6A and vRNP complex proteins had no effect on the nuclear import of PB2 or the PB1-PA heterodimer but impaired the interaction between NP and the nuclear import adaptor importin α3, thereby inhibiting the nuclear import of incoming vRNP complexes and newly synthesized NP. Moreover, KRT6A was further shown to suppress the assembly of the vRNP complex and consequently reduce viral polymerase activity. Together, our data uncover a novel role of KRT6A in counteracting the nuclear import and functions of the vRNP complex, thereby restricting the replication of IAV.
Full article
(This article belongs to the Section Animal Viruses)
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Open AccessArticle
Optimization and Validation of Universal Real-Time RT-PCR Assay to Detect Virulent Newcastle Disease Viruses
by
Ellen Ruth Alexander Morris, Megan E. Schroeder, Phelue N. Anderson, Lisa J. Schroeder, Nicholas Monday, Gabriel Senties-Cue, Martin Ficken, Pamela J. Ferro, David L. Suarez and Kiril M. Dimitrov
Viruses 2025, 17(5), 670; https://doi.org/10.3390/v17050670 - 3 May 2025
Abstract
Newcastle disease, caused by virulent strains of avian paramyxovirus 1 (APMV-1), occurs globally and has significant social and economic impact. APMV-1 is a rapidly evolving RNA virus and is genetically divided into class I and class II with almost all virulent viruses being
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Newcastle disease, caused by virulent strains of avian paramyxovirus 1 (APMV-1), occurs globally and has significant social and economic impact. APMV-1 is a rapidly evolving RNA virus and is genetically divided into class I and class II with almost all virulent viruses being of class II. The considerable genetic diversity of the virus adds complexity to maintaining the high sensitivity and specificity of molecular detection assays. The current USDA’s fusion gene rRT-PCR assay was designed for class II APMV-1 isolates with an emphasis on early-2000s US strains. Assessment with globally circulating genotypes confirmed previously described lower sensitivity (sub-genotypes VII.1.1, VII.2) and identified absence of detection (genotype XIV). An additional forward primer and two probes were designed using a comprehensive complete fusion gene sequence database. The optimized multiplex assay detected genotype XIV and improved sensitivity for sub-genotypes VII.1.1 and VII.2, with maintained sensitivity for the remaining genotypes. No near-neighbors or APMV-1 of low virulence were detected. Using field and experimental clinical samples, both the specificity and sensitivity were determined to be 100%, compared to the current assay with 100% and 93%, respectively. The new assay identifies all known chicken virulent APMV-1 genotypes with the benefit of using an exogenous internal positive control, which monitors extraction efficiency and inhibitors.
Full article
(This article belongs to the Special Issue Newcastle Disease and Other Avian Orthoavulaviruses 1)
Open AccessArticle
Plasmid-Based Reverse Genetics System Enabling One-Step Generation of Genotype 3 Hepatitis E Virus
by
Tominari Kobayashi, Takashi Nishiyama, Kentaro Yamada, Kazumoto Murata and Hiroaki Okamoto
Viruses 2025, 17(5), 669; https://doi.org/10.3390/v17050669 - 3 May 2025
Abstract
Hepatitis E virus (HEV) is a positive-sense, single-stranded RNA virus that poses a significant public health risk, yet its study is hindered by the complexity of conventional RNA-based reverse genetics systems. These systems require multiple steps, including genome cloning, in vitro transcription, and
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Hepatitis E virus (HEV) is a positive-sense, single-stranded RNA virus that poses a significant public health risk, yet its study is hindered by the complexity of conventional RNA-based reverse genetics systems. These systems require multiple steps, including genome cloning, in vitro transcription, and capping, making them labor-intensive and susceptible to RNA degradation. In this study, we developed a single-step, plasmid-based HEV expression system that enabled direct intracellular transcription of the full-length HEV genome under a cytomegalovirus immediate-early (CMV-IE) promoter. The viral genome was flanked by hammerhead (HH) and hepatitis delta virus (HDV) ribozymes to ensure precise self-cleavage and the generation of authentic 5′ and 3′ termini. This system successfully supported HEV genome replication, viral protein expression, and progeny virion production at levels comparable to those obtained using in vitro-transcribed, capped HEV RNA. Additionally, a genetic marker introduced into the plasmid construct was stably retained in progeny virions, demonstrating the feasibility of targeted genetic modifications. However, plasmid-derived HEV exhibited delayed replication kinetics, likely due to the absence of an immediate 5′ cap. Attempts to enhance capping efficiency through co-expression of the vaccinia virus capping enzyme failed to improve HEV replication, suggesting that alternative strategies, such as optimizing the promoter design for capping, may be required. This plasmid-based HEV reverse genetics system simplifies the study of HEV replication and pathogenesis and provides a versatile platform for the genetic engineering of the HEV genome.
Full article
(This article belongs to the Section Human Virology and Viral Diseases)
Open AccessReview
Australian Cool-Season Pulse Seed-Borne Virus Research: 2. Bean Yellow Mosaic Virus
by
Roger A. C. Jones
Viruses 2025, 17(5), 668; https://doi.org/10.3390/v17050668 - 3 May 2025
Abstract
Here, research on seed-borne virus diseases of cool-season pulses caused by bean yellow mosaic virus (BYMV) in Australia’s grain cropping regions since the 1940s is reviewed. A historical approach is taken towards all past studies involving the main cool-season pulse crops grown, lupin,
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Here, research on seed-borne virus diseases of cool-season pulses caused by bean yellow mosaic virus (BYMV) in Australia’s grain cropping regions since the 1940s is reviewed. A historical approach is taken towards all past studies involving the main cool-season pulse crops grown, lupin, faba bean, field pea, lentil and chickpea, and the minor ones, narbon bean, vetches and Lathyrus species. The main emphasis adopted is on describing what these studies revealed concerning BYMV biology, epidemiology and management. The field and glasshouse experimentation that enabled the development of effective phytosanitary, cultural and host resistance control strategies, supported by many image illustrations from past investigations, is emphasized. This review commences by providing brief background information and describing past studies on BYMV symptom and sequence variants, and alternative BYMV hosts. Next, as the lupin/BYMV pathosystem has been investigated in much greater depth than any other cool season pulse/BYMV pathosystem combination in Australia, what past studies using it have found is covered considerable detail under a series of nine different sub-headings. Finally, what is known about the less thoroughly investigated cool-season pulse/BYMV pathosystems, especially those involving faba bean, field pea and lentil, is reviewed under seven different sub-headings. Recommendations are provided concerning future research priorities.
Full article
(This article belongs to the Special Issue Plant Viruses and Their Vectors: Epidemiology and Control)
Open AccessArticle
Comprehensive Diagnosis of Viral Hepatitis in Spain: Bases for Implementation
by
Joaquin Cabezas, Antonio Aguilera, Federico García, Raquel Domínguez-Hernández, Araceli Casado-Gómez, Nataly Espinoza-Cámac, Miguel Ángel Casado and Javier Crespo
Viruses 2025, 17(5), 667; https://doi.org/10.3390/v17050667 - 3 May 2025
Abstract
In 2022, scientific societies agreed on a document with recommendations for a comprehensive diagnosis of viral hepatitis (B, C, and D). The aim was to evaluate the situation in Spain regarding the comprehensive diagnosis of viral hepatitis in a single blood draw before
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In 2022, scientific societies agreed on a document with recommendations for a comprehensive diagnosis of viral hepatitis (B, C, and D). The aim was to evaluate the situation in Spain regarding the comprehensive diagnosis of viral hepatitis in a single blood draw before it is recommended. A panel of experts prepared a structured survey directed at hospitals (public or private with teaching accreditation) with ≥200 beds (sent 20 October 2022, closed 1 December 2022). The response rate was 61% (79/129; 52 hospitals with >500 beds). Among the participating hospitals, all could perform tests for HBsAg, anti-HCV, and HIV serology; 94% could perform PCR testing for HCV, 63% could test for anti-HDV, and 28% could test for HDV-RNA (67% [53/79] outsourced this testing). Point-of-care (POC) testing availability was low (24%), with 84% of these tests being supervised by the reference microbiological laboratory and the results being registered in the patients’ medical history. Ninety percent of the centers carried out the diagnosis in a single step (99% HCV, 70% HBV, 48% HDV, and 44% HBV-HDV). In addition, 77% used some communication strategy when an active infection was encountered (100% HCV, 49% HBV, and 31% HDV). Only 20% had an automated system for scheduling a specialist physician appointment. Most hospitals had the means for a comprehensive diagnosis of viral hepatitis in a single sample, but <50% could test for HBV/HDV. Alerts for continuity of care were available for HCV, but not HBV or HDV. POC device implementation is important for decentralized testing.
Full article
(This article belongs to the Special Issue Advancing Hepatitis Elimination: HBV, HDV, and HCV)
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Impact of Vaccine-Elicited Anti-Spike IgG4 Antibodies on Fc-Effector Functions Against SARS-CoV-2
by
Katrina Dionne, Alexandra Tauzin, Étienne Bélanger, Yann Desfossés, Mehdi Benlarbi, Ling Niu, Guillaume Beaudoin-Bussières, Halima Medjahed, Catherine Bourassa, Josée Perreault, Marzena Pazgier, Renée Bazin and Andrés Finzi
Viruses 2025, 17(5), 666; https://doi.org/10.3390/v17050666 - 3 May 2025
Abstract
mRNA vaccines have demonstrated considerable efficacy and safety against SARS-CoV-2, limiting the pandemic burden worldwide. The emergence of new variants of concern and the decline in neutralizing activity observed several weeks post-vaccination reinforced the call for repeated mRNA vaccination. We and others have
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mRNA vaccines have demonstrated considerable efficacy and safety against SARS-CoV-2, limiting the pandemic burden worldwide. The emergence of new variants of concern and the decline in neutralizing activity observed several weeks post-vaccination reinforced the call for repeated mRNA vaccination. We and others have shown that vaccine efficacy does not exclusively rely on antibody neutralizing activites; Fc-effector functions play an important role as well. However, it is well known that long-term exposure and repeated antigen stimulation elicit the IgG4 subclass of antibodies, which are inefficient at mediating Fc-effector functions. In this regard, recent studies highlighted concerns about IgG4 induction by mRNA vaccines. Here, we explored the impact of repeated mRNA vaccination on IgG4 induction and its impact on Fc-effector functions. We observed anti-Spike IgG4 elicitation after three doses of mRNA vaccine; the antibody levels further increased with additional doses. Vaccine-elicited IgG4 preferentially bound the ancestral D614G Spike. We also observed that Breakthrough Infection (BTI) after several doses of vaccine strongly increased IgG1 levels but had no impact on IgG4 levels, thereby improving Fc-effector functions. Finally, we observed that elderly donors vaccinated with Moderna mRNA vaccines elicited higher IgG4 levels and presented lower Fc-effector functions than donors vaccinated with the Pfizer mRNA vaccine. Altogether, our results highlight the importance of monitoring the IgG subclasses elicited by vaccination.
Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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Noncanonical Poly(A) Polymerase TENT4 Drives Expression of Subgenomic Hepatitis A Virus RNAs in Infected Cells
by
You Li, Ankit Gupta, Brian N. Papas, David Aponte-Diaz, Jayden M. Harris, Ichiro Misumi, Jason K. Whitmire, Craig E. Cameron, Marcos Morgan and Stanley M. Lemon
Viruses 2025, 17(5), 665; https://doi.org/10.3390/v17050665 - 2 May 2025
Abstract
Both hepatitis B virus (HBV), an hepadnavirus with a DNA genome, and hepatitis A virus (HAV), a picornavirus, require the TRAMP-like host ZCCHC14-TENT4 complex for efficient replication. However, whereas HBV requires the nucleotidyltransferase activity of TENT4 to extend and stabilize the 3′ poly(A)
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Both hepatitis B virus (HBV), an hepadnavirus with a DNA genome, and hepatitis A virus (HAV), a picornavirus, require the TRAMP-like host ZCCHC14-TENT4 complex for efficient replication. However, whereas HBV requires the nucleotidyltransferase activity of TENT4 to extend and stabilize the 3′ poly(A) tails of mRNA transcribed from its genome, the role played by TENT4 in HAV replication is uncertain. HAV proteins are synthesized directly from its genomic RNA, which possesses a 3′ poly(A) tail, with its length and composition presumably maintained by 3Dpol-catalyzed RNA transcription during its replicative cycle. Using nanopore long-read sequencing of RNA from infected cells, we confirm here that the length of the HAV 3′ poly(A) tail is not altered by treating infected cells with RG7834, a small molecule TENT4 inhibitor with potent anti-HAV activity. Despite this, TENT4 catalytic activity is essential for HAV replication. Surprisingly, nanopore sequencing revealed a low abundance of HAV subgenomic RNAs (hsRNAs) that extend from the 5′ end of the genome to a site within the 5′ untranslated RNA (5′UTR) immediately downstream of a stem-loop to which the ZCCHC14-TENT4 complex is recruited. These hsRNAs are polyadenylated, and their abundance is sharply reduced by RG7834 treatment, implying they are likely products of TENT4. Similar subgenomic RNAs were not identified in poliovirus-infected cells. hsRNAs are present not only in HAV-infected cell culture but also in the liver of HAV-infected mice, where they represent 1–3% of all HAV transcripts, suggesting their physiological relevance. However, transfecting exogenous hsRNA into TENT4-depleted cells failed to rescue HAV replication, leaving the functional role of hsRNA unresolved. These findings reveal a novel picornaviral subgenomic RNA species while highlighting mechanistic differences in the manner in which HAV and HBV exploit the host ZCCHC4-TENT4 complex for their replication.
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(This article belongs to the Special Issue 15-Year Anniversary of Viruses)
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Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges
by
Francesco Branda, Chiara Romano, Grazia Pavia, Viola Bilotta, Chiara Locci, Ilenia Azzena, Ilaria Deplano, Noemi Pascale, Maria Perra, Marta Giovanetti, Alessandra Ciccozzi, Andrea De Vito, Angela Quirino, Nadia Marascio, Giovanni Matera, Giordano Madeddu, Marco Casu, Daria Sanna, Giancarlo Ceccarelli, Massimo Ciccozzi and Fabio Scarpaadd
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Viruses 2025, 17(5), 664; https://doi.org/10.3390/v17050664 - 1 May 2025
Abstract
Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types. HTLV-1 is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while HTLV-2
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Human T-lymphotropic viruses (HTLVs) are deltaretroviruses infecting millions of individuals worldwide, with HTLV-1 and HTLV-2 being the most widespread and clinically relevant types. HTLV-1 is associated with severe diseases such as adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), while HTLV-2 shows a lower pathogenic potential, with occasional links to neurological disorders. HTLV-3 and HTLV-4, identified in Central Africa, remain poorly characterized but are genetically close to their simian counterparts, indicating recent zoonotic transmission events. HTLVs replicate through a complex cycle involving cell-to-cell transmission and clonal expansion of infected lymphocytes. Viral persistence is mediated by regulatory and accessory proteins, notably Tax and HBZ in HTLV-1, which alter host cell signaling, immune responses, and genomic stability. Integration of proviral DNA into transcriptionally active regions of the host genome may contribute to oncogenesis and long-term viral latency. Differences in viral protein function and intracellular localization contribute to the distinct pathogenesis observed between HTLV-1 and HTLV-2. Geographically, HTLV-1 shows endemic clusters in southwestern Japan, sub-Saharan Africa, the Caribbean, South America, and parts of the Middle East and Oceania. HTLV-2 is concentrated among Indigenous populations in the Americas and people who inject drugs in Europe and North America. Transmission occurs primarily via breastfeeding, sexual contact, contaminated blood products, and, in some regions, zoonotic spillover. Diagnostic approaches include serological screening (ELISA, Western blot, LIA) and molecular assays (PCR, qPCR), with novel biosensor and AI-based methods under development. Despite advances in understanding viral biology, therapeutic options remain limited, and preventive strategies focus on transmission control. The long latency period, lack of effective treatments, and global neglect complicate public health responses, underscoring the need for increased awareness, research investment, and targeted interventions.
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(This article belongs to the Section Human Virology and Viral Diseases)
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Virucidal Approaches for Hemorrhagic Fever Viruses
by
Raymond W. Nims and M. Khalid Ijaz
Viruses 2025, 17(5), 663; https://doi.org/10.3390/v17050663 - 30 Apr 2025
Abstract
We have reviewed the primary literature on the virucidal efficacy of microbicidal active ingredients, formulated microbicides, and physical inactivation approaches (heat, irradiation) for hemorrhagic fever viruses (HFVs) (arenaviruses, filoviruses, flaviviruses, hantaviruses, nairoviruses, and phenuiviruses), and for two non-typical HFV paramyxoviruses. As each of
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We have reviewed the primary literature on the virucidal efficacy of microbicidal active ingredients, formulated microbicides, and physical inactivation approaches (heat, irradiation) for hemorrhagic fever viruses (HFVs) (arenaviruses, filoviruses, flaviviruses, hantaviruses, nairoviruses, and phenuiviruses), and for two non-typical HFV paramyxoviruses. As each of these HFVs are large, lipid-enveloped RNA viruses, their susceptibilities to virucidal agents are informed by the so-called hierarchy of susceptibility of pathogens to microbicides. The unique susceptibility of lipid-enveloped viruses to most classes of microbicides is based on the common mechanisms of action of envelope-disrupting microbicides. Despite this, due to the relatively great lethality of these viruses, it is prudent (where possible) to confirm the expected efficacies of inactivation approaches in testing involving the HFVs themselves (as opposed to less lethal surrogate viruses) using field-relevant methods. Empirical data for virucidal activities of microbicidal active ingredients, formulated microbicides, and physical inactivation approaches, such as heat, ultraviolet light, and gamma irradiation, that were collected specifically for HFVs have been reviewed and summarized in this paper. These empirical data for surface and hand hygiene approaches, liquid inactivation approaches, and approaches for rendering diagnostic samples safe to handle inform non-pharmaceutical interventions intended to mitigate transmission risk associated with these HFVs.
Full article
(This article belongs to the Special Issue Viral Hemorrhagic Disease)
Open AccessReview
HPV-Driven Head and Neck Cancer: The European Perspective
by
Wojciech Golusiński, Ewelina Golusińska-Kardach, Piotr Machczyński and Mateusz Szewczyk
Viruses 2025, 17(5), 662; https://doi.org/10.3390/v17050662 - 30 Apr 2025
Abstract
Head and neck squamous-cell carcinoma (HNSCC) has long been associated with tobacco and alcohol use. In the last two decades, however, human papillomavirus (HPV) infection has emerged as an important driver of these cancers, particularly in the oropharynx. The eighth edition of the
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Head and neck squamous-cell carcinoma (HNSCC) has long been associated with tobacco and alcohol use. In the last two decades, however, human papillomavirus (HPV) infection has emerged as an important driver of these cancers, particularly in the oropharynx. The eighth edition of the American Joint Committee on Cancer (AJCC) staging system now defines HPV+ and HPV−OPSCC as separate entities. Although our understanding of HPV+ HNSCC continues to improve, it can be challenging to keep up to date with the growing body of evidence. In this context, the present narrative review was carried out to provide an overview of HPV-driven head and neck cancer, with an emphasis on Europe. We review the latest evidence on epidemiology, diagnosis, and treatment, including recent trends towards treatment de-intensification and future directions.
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(This article belongs to the Section Human Virology and Viral Diseases)
Open AccessArticle
Key Laboratory Markers for Early Detection of Severe Dengue
by
Kumar Sivasubramanian, Raj Bharath R, Leela Kakithakara Vajravelu, Madan Kumar D and Aritra Banerjee
Viruses 2025, 17(5), 661; https://doi.org/10.3390/v17050661 - 30 Apr 2025
Abstract
Dengue virus is the most prevalent arthropod-borne viral disease in humans. Severe dengue, defined by hemorrhagic fever and dengue shock syndrome, can develop quickly in people who have warning indications such as abdominal pain, mucosal bleeding, and a significant decrease in platelet count.
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Dengue virus is the most prevalent arthropod-borne viral disease in humans. Severe dengue, defined by hemorrhagic fever and dengue shock syndrome, can develop quickly in people who have warning indications such as abdominal pain, mucosal bleeding, and a significant decrease in platelet count. Laboratory markers such as hematocrit, platelet count, liver enzymes, and coagulation tests are critical for early diagnosis and prognosis. This retrospective study was carried out from January 2023 to December 2024 at a super-specialty tertiary care hospital. There were 283 adult patients with dengue with warning signs, who were categorized into 102 with platelet transfusion and 181 with no platelet transfusion. Data on patient demographics, clinical history, laboratory values, and radiological findings were systematically obtained from hospital records at the time of admission. Laboratory parameters such as white blood cell (OR = 2.137), hemoglobin (OR = 2.15), aPTT (OR = 5.815), AST2/ALT (OR = 2.431), platelet count (OR = 26.261) and NS1 (OR = 4.279) were found to be significantly associated (p < 0.01) with platelet transfusion. Similarly, an increased prothrombin time (OR = 2.432) contributed to prolonged hospital stays and the presence of ascites (OR = 5.059), gallbladder wall thickening (OR = 4.212), and pleural effusion (OR = 2.917), contributing to the severity of the dengue infection. These significant laboratory markers help with identifying patients with dengue who may develop severe dengue, requiring platelet transfusion, thereby prioritizing patient care and enabling the implementation of targeted interventions.
Full article
(This article belongs to the Special Issue Arboviruses and Global Health: A PanDengue Net Initiative)
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Open AccessBrief Report
Human Herpesvirus 1 Associated with Epizootics in Belo Horizonte, Minas Gerais, Brazil
by
Gabriela Fernanda Garcia-Oliveira, Mikaelly Frasson Biccas, Daniel Jacob, Marcelle Alves Oliveira, Ana Maria de Oliveira Paschoal, Pedro Augusto Alves, Cecília Barreto, Daniel Ambrósio da Rocha Vilela, Érika Procópio Tostes Teixeira, Thiago Lima Stehling, Thais Melo Mendes, Marlise Costa Silva, Munique Guimarães Almeida, Ivan Vieira Sonoda, Érica Munhoz Mello, Francisco Elias Nogueira Gama, Kathryn A. Hanley, Nikos Vasilakis and Betania Paiva Drumond
Viruses 2025, 17(5), 660; https://doi.org/10.3390/v17050660 (registering DOI) - 30 Apr 2025
Abstract
Human activity in sylvatic environments and resulting contact with wildlife, such as non-human primates (NHPs), can lead to pathogen spillover or spillback. Both NHPs and humans host a variety of herpesviruses. While these viruses typically cause asymptomatic infections in their natural hosts, they
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Human activity in sylvatic environments and resulting contact with wildlife, such as non-human primates (NHPs), can lead to pathogen spillover or spillback. Both NHPs and humans host a variety of herpesviruses. While these viruses typically cause asymptomatic infections in their natural hosts, they can lead to severe disease or even death when they move into novel hosts. In early 2024, deaths of Callithrix penicillata, the black-tufted marmoset, were reported in an urban park in Belo Horizonte, Minas Gerais, Brazil. The epizootic was investigated in collaboration with CETAS/IBAMA and the Zoonoses Department of Belo Horizonte. Nine marmoset carcasses and four sick marmosets were found in the park; the latter exhibited severe neurological symptoms and systemic illness before succumbing within 48 h. Carcasses were tested for rabies virus and were all negative, and necropsy findings revealed widespread organ damage. In addition, the samples were tested for yellow fever virus, with negative results. Finally, molecular testing, viral isolation, and phylogenetic analysis demonstrated human herpesvirus 1 (HHV-1) as the causative agent. The likely source of infection was human-to-marmoset transmission, facilitated by close interactions such as feeding and handling. This study highlights the risks of pathogen spillover between humans and nonhuman primates, emphasizing the need for enhanced surveillance and public awareness to mitigate future epizootics.
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(This article belongs to the Section Animal Viruses)
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Open AccessCommunication
Novel Minimal Absent Words Detected in Influenza A Virus
by
Elif Zülal Bigiş, Elif Yıldız, Anna Tagka, Athanasia Pavlopoulou, George P. Chrousos and Styliani Geronikolou
Viruses 2025, 17(5), 659; https://doi.org/10.3390/v17050659 - 30 Apr 2025
Abstract
Influenza is a communicable disease caused by RNA viruses. Strains A (affecting animals, humans), B (affecting humans), C (affecting rarely humans and pigs), and D (affecting cattle) comprise a variety of substrains each. Influenza A strain, affecting both humans and animals, is considered
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Influenza is a communicable disease caused by RNA viruses. Strains A (affecting animals, humans), B (affecting humans), C (affecting rarely humans and pigs), and D (affecting cattle) comprise a variety of substrains each. Influenza A strain, affecting both humans and animals, is considered the most infectious, causing pandemics. There is an emerging need for the accurate classification of the different influenza A virus (IAV) subtypes, elucidating their mode of infection, as well as their fast and accurate diagnosis. Notably, in recent years, oligomeric sequences (words) that are present in the pathogen genomes and entirely absent from the host human genome were suggested to provide robust biomarkers for virus classification and rapid detection. To this end, we performed updated phylogenetic analyses of the IAV hemagglutinin genes, focusing on the sub H1N1 and H5N1. More importantly, we applied in silico methods to identify minimum length “words” that exist consistently in the IAV genomes and are entirely absent from the human genome; these sequences identified in our current analysis may represent minimal signatures that can be utilized to distinguish IAV from other influenza viruses, as well as to perform rapid diagnostic tests.
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(This article belongs to the Special Issue Coronaviruses and Influenza Viruses: Evolution, Cross-Species Transmission, and Recombination)
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Open AccessArticle
Genomic and Phenotypic Characterization of a Novel Virulent Strain of Cyvirus cyprinidallo2 Originating from an Outbreak in The Netherlands
by
Bo He, Arun Sridhar, Marc Thiry, Olga Haenen, Alain F. C. Vanderplasschen and Owen Donohoe
Viruses 2025, 17(5), 658; https://doi.org/10.3390/v17050658 - 30 Apr 2025
Abstract
Cyvirus cyprinidallo2 (CyHV-2) is the causative agent of herpesviral hematopoietic necrosis in several economically important farmed freshwater fish species of the genus Carassius. Despite several CyHV-2 strains being isolated and fully sequenced, there is a lack of detailed characterization and consistent
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Cyvirus cyprinidallo2 (CyHV-2) is the causative agent of herpesviral hematopoietic necrosis in several economically important farmed freshwater fish species of the genus Carassius. Despite several CyHV-2 strains being isolated and fully sequenced, there is a lack of detailed characterization and consistent information on strains that exhibit high virulence in adult goldfish through viral challenge by immersion, particularly in the context of European strains and host populations. Strains that can cause highly virulent disease via this inoculation route are much more compatible with experimental designs that are representative of natural infection; thus, their utilization provides greater biological relevance. Consequently, in this study, we isolated three novel strains of CyHV-2 (designated NL-1, NL-2, and NL-3), originating from outbreaks in The Netherlands. Full-length genome sequencing and phylogenetic analyses revealed that these newly isolated strains are distinct from known strains and from each other. Significant differences were observed between the strains, in terms of in vitro growth kinetics, with NL-2 exhibiting stable passaging and superior fitness in vitro. Importantly, the challenge of adult Shubunkin goldfish with the NL-2 strain via immersion (2000 PFU/mL) induced an average mortality of ~40%, while parallel experiments with the CyHV-2 reference strain ST-J1 resulted in no mortality. Taken together, this study represents the characterization of a new CyHV-2 in vivo infection model, much more compatible with experimental designs that are required to be representative of natural infection. This model will be extremely useful in many aspects of CyHV-2 research in the future. Importantly, the genetic and phenotypic characterization performed in this study generates hypotheses on the potential roles of CyHV-2 genes in adaptation of the virus in vitro or in vivo.
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(This article belongs to the Special Issue Aquatic Animal Viruses and Antiviral Immunity)
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Open AccessArticle
Prevalence of Acute Gastroenteritis Enteropathogens Among Hospitalized Children in Jordan: A Single-Center Study
by
Ashraf I. Khasawneh, Nisreen Himsawi, Ashraf Sammour, Faten A. Bataineh, Mohammad H. Odeh, Mayar S. Alhieh, Nawal S. Hijjawi, Mohammad Wahsheh, Hafez Al-Momani, Moureq R. Alotaibi, Sofian Al Shboul and Tareq Saleh
Viruses 2025, 17(5), 657; https://doi.org/10.3390/v17050657 - 30 Apr 2025
Abstract
Background and objectives: Acute gastroenteritis (AGE) remains a significant cause of morbidity in children, particularly in low- and middle-income countries. Viral pathogens, including rotavirus (RoV), norovirus (NoV), and adenovirus (HAdV), are among the leading causes of AGE. This study aimed to determine the
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Background and objectives: Acute gastroenteritis (AGE) remains a significant cause of morbidity in children, particularly in low- and middle-income countries. Viral pathogens, including rotavirus (RoV), norovirus (NoV), and adenovirus (HAdV), are among the leading causes of AGE. This study aimed to determine the prevalence of viral, bacterial, and parasitic enteric pathogens associated with AGE among hospitalized children in Northern Jordan. Materials and Methods: A total of 195 stool samples were collected from hospitalized children with AGE during the winter seasons of 2022–2024. Multiplex real-time qPCR assays were performed to detect common pathogens. The prevalence of each pathogen was determined, and co-infections were analyzed. Clinical symptoms, demographic characteristics, and associations between specific pathogens and disease severity were evaluated. Results: Viral pathogens were the predominant cause of AGE, with NoV detected in 53 cases (27.2%; of which 19.0% were NoV GI and 8.2% NoV GII), followed by RoV (24.1%), HAdV (20.0%), HAstV (13.3%), and SaV (12.3%). Co-infections were observed in several cases, particularly among viral infections evoked by RoV, HAdV, and NoV GI. Bacterial and parasitic infections were less prevalent, with Salmonella and Campylobacter spp. detected in 23.1% and 13.8%, respectively. Additionally, Cryptosporidium was identified in two cases (0.5%). Conclusions: Viral pathogens, particularly NoV, RoV, and HAdV, are the leading causes of AGE among hospitalized children in Jordan. Co-infections among viral pathogens were common, whereas bacterial and parasitic infections played a limited role in the disease burden. These findings emphasize the importance of continued surveillance and vaccination efforts, particularly for RoV, to reduce AGE-related hospitalizations in children.
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(This article belongs to the Section Human Virology and Viral Diseases)
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Open AccessArticle
The Junction Between nsp1β and nsp2 in the Porcine Reproductive and Respiratory Syndrome Virus Genome Is a New Site for the Insertion and Expression of Foreign Genes
by
Changguang Xiao, Yafang Lin, Hailong Zhang, Zongjie Li, Ke Liu, Beibei Li, Donghua Shao, Yafeng Qiu, Zhiyong Ma and Jianchao Wei
Viruses 2025, 17(5), 656; https://doi.org/10.3390/v17050656 - 30 Apr 2025
Abstract
Porcine reproductive and respiratory syndrome virus (PRRSV) is considered a promising viral vector for the expression and delivery of foreign genes for the development of a new generation of multi-valent vaccines against PRRSV and other porcine viruses, as well as for analyses of
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Porcine reproductive and respiratory syndrome virus (PRRSV) is considered a promising viral vector for the expression and delivery of foreign genes for the development of a new generation of multi-valent vaccines against PRRSV and other porcine viruses, as well as for analyses of the immune response against PRRSV and anti-PRRSV component screening. In the present study, the junction site between nsp1β and nsp2 in the PRRSV genome was tested for the insertion and expression of foreign genes. Three foreign genes, including eGFP, iLOV3, and TEVp, were inserted into the intergenic junction between nsp1β and nsp2 and expressed by the respective recombinant PRRSVs (rPRRSV-SH01-eGFP, rPRRSV-SH01-iLOV3, and rPRRSV-SH01-TEVp) in vitro in mammalian cells. Analysis of the growth kinetics of the rescued recombinant PRRSVs showed no significant differences between the recombinant PRRSVs and their parental viruses. The inserted genes were consistently present in the viral genome during serial passage in vitro (for at least 20 passages). In addition, rPRRSV-SH01-eGFP can be used as a reporter virus for rapid detection of neutralizing antibodies against PRRSV through a fluorescent focus unit reduction-based assay. These data demonstrate that the junction between nsp1β and nsp2 is a new site that is suitable for the insertion and expression of foreign genes, providing a new option to express and deliver foreign genes using PRRSV-based vectors for different purposes, such as the development of multi-valent vaccines against PRRSV and other porcine viruses.
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(This article belongs to the Special Issue Porcine Viruses 2025)
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Open AccessArticle
Sequencing of One Unique Recombinant CRF85_BC/CRF01_AE Genome and Two Partial Genomes from Ningxia, China
by
Yufeng Li, Jianxin Pei, Xiaohong Zhu, Yichang Liu, Xiaofa Ma, Dongzhi Yang and Zhonglan Wu
Viruses 2025, 17(5), 655; https://doi.org/10.3390/v17050655 - 30 Apr 2025
Abstract
The recent emergence of new HIV-1 recombinant strains presents a new challenge to the control of HIV-1/AIDS and the development of an effective vaccine. We employed a near full-length genomic sequence analysis of a newly identified CRF85_BC recombinant strain in Ningxia, China, to
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The recent emergence of new HIV-1 recombinant strains presents a new challenge to the control of HIV-1/AIDS and the development of an effective vaccine. We employed a near full-length genomic sequence analysis of a newly identified CRF85_BC recombinant strain in Ningxia, China, to determine its recombination pattern. Blood samples were collected from HIV-infected or AIDS patients in Ningxia in 2023. CRF85_BC subtype strains were detected from three samples using an in-house method, and one sample’s near full-length genome sequence was also obtained. MEGA11, jpHMM, and Simplot software were used to identify subtypes and analyze recombination patterns. Neighbor-joining phylogenetic tree analysis showed that HIV-1 pol region sequences of three samples were CRF85_BC subtypes. One near full-length genome sequence of the recombinant strain was obtained, and jpHMM preliminarily judged that the recombinant strain was inserted with two subtype B fragments and two CRF01_AE fragments based on subtype C as the backbone. Further analysis using Simplot software revealed that the recombinant strain was the second-generation recombinant strain of CRF85_BC and CRF01_AE, and the recombination mode was based on the full-length genome of CRF85_BC, and CRF01_AE gene fragments that were inserted at positions 7365–8279 and 8431–9492, respectively. The results of the fragment phylogenetic tree verified its accuracy. One CRF01_AE and CRF85_BC second-generation recombinant strain was found in HIV-1 infected people in Ningxia, indicating that new HIV-1 recombinant strains continuously emerge and circulate in this region. Genomic surveillance of these recombinants should inform targeted interventions, such as prioritized contact tracing, to mitigate the formation of transmission clusters.
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(This article belongs to the Section Human Virology and Viral Diseases)
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