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Volume 18
Issue 3
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Viruses, Volume 18, Issue 3 (March 2026) – 125 articles

Cover Story (view full-size image): Vesicular stomatitis virus (VSV) is a promising oncolytic virus whose replication is tightly linked to host cell metabolism. In cancer cells, such as glioblastoma, metabolic pathways including glycolysis, the pentose phosphate pathway (PPP), and glutaminolysis are extensively rewired to support growth and survival. Here, we demonstrate that VSV replication critically depends on glycolytic flux, glutamine metabolism, and intracellular NAD+ availability. Pharmacological inhibition of these pathways suppresses viral replication, while restoration of NAD+ rescues viral growth. Notably, depletion of G6PD enhances replication, revealing complex metabolic regulation. These findings highlight a redox-centric framework governing VSV replication and provide insights for optimizing oncolytic virotherapy through metabolic targeting. View this paper
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16 pages, 3518 KB  
Article
Phage Stability Across Conditions: Ensuring Accurate Use of Viral Surrogates in Antiviral Testing
by Sabine Poelzl and Clemens Kittinger
Viruses 2026, 18(3), 398; https://doi.org/10.3390/v18030398 - 23 Mar 2026
Viewed by 700
Abstract
Bacteriophages can serve as practical surrogates for human viruses in laboratory tests. They share key structural characteristics but are non-pathogenic and can be handled under lower biosafety conditions. This facilitates experiments on persistence, disinfection and materials-testing while reducing time, costs and logistical requirements. [...] Read more.
Bacteriophages can serve as practical surrogates for human viruses in laboratory tests. They share key structural characteristics but are non-pathogenic and can be handled under lower biosafety conditions. This facilitates experiments on persistence, disinfection and materials-testing while reducing time, costs and logistical requirements. However, phage survival strongly depends on many factors including environmental conditions, such as temperature and relative humidity (RH). This study investigates the survival of bacteriophages Phi6, Qbeta and MS2 under different incubation conditions including storage on a surface, in liquid and in the fridge. Standardized ISO protocols for antimicrobial surface testing and extensions were applied. All phages demonstrated good survival in liquid, although stability was temperature-dependent. At refrigerator temperatures, phages remained stable for several months with only minor reduction in the initial titer. At 50 °C, the two non-enveloped phages survived for up to one week, whereas the enveloped phage Phi6 was inactivated within one day. On glass surfaces, Phi6 exhibited reduced stability and was detectable only up to one week at 25 °C and >90% RH. Qbeta and MS2 survived from several days at 50 °C to two to seven days at 37 °C, depending on RH, and remained detectable at 25 °C regardless of humidity. These differences highlight the importance of carefully selecting incubation conditions, as these directly affect phage stability. In particular, unsuitable conditions for antimicrobial testing may cause phage inactivation and thus lead to false-positive results. Therefore, it is essential to define the conditions under which each phage produces reliable results. Full article
(This article belongs to the Section Bacterial Viruses)
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13 pages, 1945 KB  
Article
Distribution of Ugandan Passiflora Virus (Potyvirus passiflorafricanse) in Major Passion Fruit Growing Areas in Rwanda
by Esperance Munganyinka, Bancy W. Waweru, Marie Claire Kanyange, Josiane Umubyeyi, Ghislain Niyonteze, Lydie Kankundiye and Melanie Mukashimwe
Viruses 2026, 18(3), 397; https://doi.org/10.3390/v18030397 - 23 Mar 2026
Viewed by 653
Abstract
Passion fruit (Passiflora edulis Sims) is an important economic fruit crop in Rwanda grown for both domestic consumption and export markets. However, viral diseases pose a significant threat to passion fruit production. Among these, passion fruit woodiness disease (PWD) is the most [...] Read more.
Passion fruit (Passiflora edulis Sims) is an important economic fruit crop in Rwanda grown for both domestic consumption and export markets. However, viral diseases pose a significant threat to passion fruit production. Among these, passion fruit woodiness disease (PWD) is the most destructive, causing yield losses of up to 100%. A survey was carried out to assess the distribution of Ugandan passiflora virus (UPV; Potyvirus passiflorafricanse) in major passion fruit growing areas. UPV is one of the major viruses known to cause PWD. The incidence of viral symptoms observed in the field did not differ significantly among districts, ranging from 81% in Rusizi to 100% in Rwamagana. However, mean symptom severity scores varied significantly between districts, with the highest severity recorded in Kayonza (3.1) and the lowest in Rulindo (1.9). Serological analysis detected potyviruses in 44% of the total samples (n = 216), including 43% of symptomatic (n = 144) and 47% of asymptomatic (n = 72) leaf samples collected from passion fruit fields. Further analysis using Reverse-Transcription Polymerase Chain Reaction (RT-PCR) detected UPV in 56% of symptomatic (n = 126) and 53% of asymptomatic (n = 60) samples, corresponding to 55% of the total samples tested (n = 186). The virus was present in all surveyed districts, with UPV infection prevalence of 89% in Rusizi, 75% in Rwamagana, 74% in Karongi, 59% in Nyamagabe, 44% in Nyaruguru, 38% in Kayonza, and 30% in both Gakenke and Rulindo. Fifteen partial coat-protein gene sequences for the Rwandan isolates were obtained. The newly described Rwandan isolates shared 97–99% nucleotide (nt) identity with one another, 89–94% with previously reported Rwandan isolates, 81–97% with Ugandan isolates, and 80–82% with Kenyan UPV isolates, suggesting that the Rwandan virus population is relatively homogenous. Genetic distances among the 15 new UPV isolates and previously reported Rwandan, Ugandan, and Kenyan isolates were very short (0.01–0.03), indicating high sequence similarity. All Rwandan isolates clustered into a single major clade, together with some Ugandan and Kenyan isolates. This close genetic relationship suggests a common ancestry and the regional spread of a single dominant UPV lineage. These findings highlight the need to reinforce seed and planting-material certification systems, as well as the need to enhance farmer capacity through targeted training on viral disease identification and management practices. This is vital to limiting the spread of viral diseases that threaten income security among smallholder passion fruit farmers. Full article
(This article belongs to the Special Issue Economically Important Viruses in African Crops)
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22 pages, 1119 KB  
Article
High Seroprevalence of Bluetongue Virus Serotype 3 in Belgian Cattle and Sheep After the 2024 Epidemic
by Mickaël Cargnel, Xavier Simons, Ilse De Leeuw, Nick De Regge and Jean-Baptiste Hanon
Viruses 2026, 18(3), 396; https://doi.org/10.3390/v18030396 - 22 Mar 2026
Viewed by 851
Abstract
To monitor the epidemiological situation of bluetongue virus (BTV) in Belgium, a national surveillance programme was conducted during the 2024–2025 winter season. The objective was to estimate the apparent seroprevalence of BTV-3 following the 2023–2024 epidemic and to prove the absence of active [...] Read more.
To monitor the epidemiological situation of bluetongue virus (BTV) in Belgium, a national surveillance programme was conducted during the 2024–2025 winter season. The objective was to estimate the apparent seroprevalence of BTV-3 following the 2023–2024 epidemic and to prove the absence of active circulation of other BTV serotypes in mixed herds (cattle and sheep). A total of 2551 cattle and 1458 sheep were sampled across Belgium. Serological analyses were performed using ELISA, and molecular detection of BTV-3, BTV-8, and BTV-12 was conducted by RT-qPCR. The majority of cattle and sheep herds showed evidence of exposure to BTV-3, with a very high herd-level apparent seroprevalence (100%; 95% CI: 96.2–100% in cattle and 98.9%; 95% CI: 93.8–99.8% in sheep). Apparent within-herd seroprevalence was also high in cattle (94.6%; 95% CI: 91.8–96.5%) and sheep (85.5%; 95% CI: 80.4–89.5%). No evidence of active circulation of BTV-8 or BTV-12 was detected. A moderate significant positive correlation between Ct values and sampling date was observed both for bovine and ovine samples, consistent with a progressive decline in detectable BTV RNA during winter in the absence of vector activity. Full article
(This article belongs to the Special Issue Bluetongue, Epizootic Haemorrhagic Disease, and Other Emerging Orbiviruses, 2nd Edition)
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16 pages, 5272 KB  
Article
Metagenomics Analysis of Viruses Associated with Cassava Brown Streak Disease in Kenya
by Florence M. Munguti, Katherine LaTourrette, Gonçalo Silva, Solomon Maina, Dora C. Kilalo, Isaac Macharia, Agnes W. Mwango’mbe, Evans N. Nyaboga and Hernan Garcia-Ruiz
Viruses 2026, 18(3), 395; https://doi.org/10.3390/v18030395 - 21 Mar 2026
Viewed by 825
Abstract
Cassava brown streak disease (CBSD), caused by cassava brown streak virus (CBSV; Ipomovirus brunusmanihotis) and Ugandan cassava brown streak virus (UCBSV; Ipomovirus manihotis) (family Potyviridae, genus Ipomovirus), is increasingly becoming a threat to cassava production in several parts of [...] Read more.
Cassava brown streak disease (CBSD), caused by cassava brown streak virus (CBSV; Ipomovirus brunusmanihotis) and Ugandan cassava brown streak virus (UCBSV; Ipomovirus manihotis) (family Potyviridae, genus Ipomovirus), is increasingly becoming a threat to cassava production in several parts of Africa, especially in Eastern, Central and Southern Africa. In Kenya, the disease continues to wreak havoc on cassava production leading to a significant reduction in crop yields and economic losses of up to USD 1 billion. Variation in virus populations make the control of CBSD challenging as virus genomic variation can affect the accuracy of diagnostic tests, lead to resistance breaking isolates and jeopardize strategies of breeding for resistance. CBSV and UCBSV populations obtained from cassava fields in Kenya were characterized. In total, 44 new complete sequences of CBSV and UCBSV were assembled and 40 sequences successfully submitted to GenBank. Single Nucleotide Polymorphism (SNP) analysis revealed that the cylindrical inclusion protein (CI) is the most stable region across the genome of CBSV and UCBSV. In contrast, protein 1 (PI) and the coat protein (CP) were the most hypervariable regions. Phylogenetic analysis showed three major geographical groupings for both UCBSV and CBSV isolates, suggesting a continued spread of the viruses through human-mediated movement of infected planting materials. The data obtained in this study can support the development of disease management strategies through improved molecular diagnostic tests and targets for breeding for resistance against CBSD. Full article
(This article belongs to the Special Issue Viroinformatics and Viral Diseases)
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13 pages, 246 KB  
Article
Seroepidemiology and Reactivation Rates of Cytomegalovirus in HIV-Positive Patients in Istanbul: A Retrospective Analysis
by Derya Sevimli Saydan, Murat Hakan Kir, Muammer Osman Köksal, Kutay Sarsar, Arat Hulikyan, Atahan Cagatay, Mehmet Demirci, Pınar Soguksu, Eray Yurtseven, Serra Zeynep Akkoyunlu, Sevim Meşe, Ali Agacfidan and Hayriye Kirkoyun Uysal
Viruses 2026, 18(3), 394; https://doi.org/10.3390/v18030394 - 21 Mar 2026
Viewed by 819
Abstract
Cytomegalovirus (CMV) remains a major opportunistic pathogen in individuals with HIV. The aim of this study was to investigate the seroprevalence and reactivation rates of CMV among HIV-positive individuals. A total of 300 people with HIV presenting to the Istanbul Faculty of Medicine [...] Read more.
Cytomegalovirus (CMV) remains a major opportunistic pathogen in individuals with HIV. The aim of this study was to investigate the seroprevalence and reactivation rates of CMV among HIV-positive individuals. A total of 300 people with HIV presenting to the Istanbul Faculty of Medicine were enrolled. Serological assessments were performed using enzyme-linked immunosorbent assay (ELISA), while molecular analyses were conducted through PCR-based methods. Sociodemographic and clinical characteristics of the patients were also evaluated. Of the participants, 90% were male, with an age range of 18–76 years. Serological testing demonstrated CMV IgG positivity in 292 patients (97.3%) and CMV IgM positivity in 11 patients (4.07%). CMV DNA was detected in 91 patients (30.3%) by molecular assays, with viral loads ranging from <150 to 2,404,678 copies/mL. CMV DNA positivity was significantly more frequent in older patients (p < 0.05) and was associated with lower CD4+ T lymphocyte counts. CMV disease was identified in 50 patients (16.7%), with organ involvement (64%) representing the most common clinical manifestation. CMV seropositivity is remarkably high in HIV-positive individuals, and reactivation rates are increased, particularly in older patients and those with advanced immunosuppression. These findings underscore the clinical relevance of routine CMV surveillance in the management of HIV infection. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
14 pages, 708 KB  
Article
Disentangling SARS-CoV-2 Sustained Viremia Cases: Evolution, Persistence and Reinfection
by Brunna M. Alves, Filipe R. R. Moreira, Marianne M. Garrido, Pedro S. de Carvalho, Élida M. de Oliveira, Caroline C. de Sá, James Arthos, Claudia Cicala, João P. B. Viola, Livia R. Goes, Juliana D. Siqueira and Marcelo A. Soares
Viruses 2026, 18(3), 393; https://doi.org/10.3390/v18030393 - 21 Mar 2026
Viewed by 798
Abstract
Based on the follow-up of patients who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, several reports of people who re-tested positive have been described. This may result from viral reactivation, true reinfection, superinfection, or an initial infection by more than [...] Read more.
Based on the follow-up of patients who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, several reports of people who re-tested positive have been described. This may result from viral reactivation, true reinfection, superinfection, or an initial infection by more than one virus (multiple infection). These scenarios can only be correctly distinguished through viral quasispecies analysis. Herein, 26 cancer patients under extended follow-up for SARS-CoV-2 infection were submitted to multiple longitudinal analyses through nucleic acid isolation, PCR amplification and high-throughput sequencing. SARS-CoV-2 classification and the definition of cases as persistent or repeated infections were based on phylogenetic reconstruction. Supported by their viral complete genomes and intrahost quasispecies over time, the different scenarios were identified. Nine confirmed and 12 plausible persistence cases were identified. Virus evolution dynamics in the intrahost population from patients with persistent infection was shown for the first time. Regarding reinfection, three confirmed and two plausible cases were identified, including one case of multiple infection. Altogether, this is the first study that analyzes the plethora of SARS-CoV-2 within-host minor variants and describes reinfections, multiple infections and viral evolution across time in cancer patients, contributing to the understanding of SARS-CoV-2’s within-host population dynamics in the natural history of COVID-19. Full article
(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 4th Edition)
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16 pages, 322 KB  
Review
Bacteriophages as Antibacterial Agents Against Bovine Pathobionts Associated with Foodborne Human Morbidity
by Mary Garvey
Viruses 2026, 18(3), 392; https://doi.org/10.3390/v18030392 - 20 Mar 2026
Viewed by 805
Abstract
Rates of foodborne infectious disease are increasing globally. The One Health zoonoses report shows increasing cases of shigatoxigenic Escherichia coli, campylobacteriosis, salmonellosis and listeriosis in the last 5 years. The ESKAPE pathogens are the top priority due to their alarming rate of [...] Read more.
Rates of foodborne infectious disease are increasing globally. The One Health zoonoses report shows increasing cases of shigatoxigenic Escherichia coli, campylobacteriosis, salmonellosis and listeriosis in the last 5 years. The ESKAPE pathogens are the top priority due to their alarming rate of resistance to broad-spectrum beta-lactams, carbapenems, glycopeptides, fluoroquinolones, aminoglycosides and biocide solutions. Research assessing alternative biocontrol options highlight the advantages of bacteriophages in the control of resistant bacterial species. Phage formulations including ListShieldTM and SalmoFreshTM have gained FDA approval for food production. As biocontrol agents, however, phages are limited by their specificity in a multispecies environment, the presence of environmental variables and bacterial resistance mechanisms. Genetic modification and the use of phage cocktails aim to overcome such limitations. Future research is warranted in a harmonised approach supported by a defined legal framework to establish best formulation and exposure protocols. This review discusses phages as biocontrol agents in the control of high-risk pathobionts associated with foodborne illness. Pathobionts associated with bovine livestock are discussed due to the morbidity and incidence of disease associated with such pathogens. Full article
(This article belongs to the Special Issue Dual Nature of Bacteriophages: Friends or Enemies in the Food Industry?—2nd Edition)
16 pages, 1339 KB  
Case Report
Antiviral Treatment for Congenital Cytomegalovirus Infection in Extremely Preterm Newborn: A Case Report and Literature Review
by Giovanni Boscarino, Giusy Davino, Silvia Pezzoni, Mara Corradi, Maria Carmela Pera, Susanna Esposito and Enzo Romanini
Viruses 2026, 18(3), 391; https://doi.org/10.3390/v18030391 - 20 Mar 2026
Viewed by 956
Abstract
Background: Congenital cytomegalovirus (cCMV) infection is one of the most common congenital infections worldwide and the leading cause of non-genetic sensorineural hearing loss. Although less frequent in preterm infants, cCMV may significantly worsen outcomes in an already vulnerable population. The risks and benefits [...] Read more.
Background: Congenital cytomegalovirus (cCMV) infection is one of the most common congenital infections worldwide and the leading cause of non-genetic sensorineural hearing loss. Although less frequent in preterm infants, cCMV may significantly worsen outcomes in an already vulnerable population. The risks and benefits of antiviral therapy in extremely preterm neonates remain unclear, as this group is largely excluded from clinical trials. Case presentation: We report a case of symptomatic cCMV infection in an extremely preterm infant born at 26 weeks and 2 days of gestation to a mother with primary CMV infection during the second trimester. High CMV viral loads were detected in urine and plasma shortly after birth. On day of life (DOL) 3, respiratory deterioration required intubation, with radiological findings consistent with CMV pneumonia and positive bronchoaspirate samples. Intravenous ganciclovir was initiated on DOL 16 and administered for six weeks, followed by oral valganciclovir for six months. Treatment was associated with a favourable clinical and virological response and no significant hematological toxicity. Ophthalmologic and audiological evaluations were normal. Neurodevelopmental assessment with Bayley III at one year of corrected age demonstrated age-appropriate performance across all domains. Discussion: A structured literature review identified 10 case reports, including 13 extremely preterm infants treated for cCMV infection. Antiviral dosing regimens were heterogeneous. The most frequent manifestations prompting treatment were laboratory abnormalities (92.3%), particularly thrombocytopenia and leukopenia or neutropenia. Neuroimaging abnormalities and intrauterine growth restriction or small for gestational age were each reported in 53.8% of cases. Long-term neurodevelopmental outcomes were normal in 38.5% of infants. Conclusions: Antiviral therapy for cCMV infection with ganciclovir and valgancyclovir in premature neonates is feasible and safe with careful monitoring, and appears to provide benefits. Nevertheless, well-designed studies that include pharmacokinetics and pharmacodynamics, virologic monitoring, and long term outcomes of development, vision and hearing are urgently needed. Full article
(This article belongs to the Special Issue Congenital Cytomegalovirus Infection, 3rd Edition)
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13 pages, 3522 KB  
Article
Synergistic Inhibition of Porcine Reproductive and Respiratory Syndrome Virus by a Bifunctional 5′-PPP miRNA Combining RIG-I Activation with Sequence-Specific Viral Targeting
by Zihang Song, Jiabao Hou, Feng Guo, Longping Chen, Chudong Wang, Xinjie Guo, Ping Li, Wenlong Shen, Jiajun Yang, Hongxu Zhong, Hanlu Zhang, Yan Zhang, Enqi Du and Zhihu Zhao
Viruses 2026, 18(3), 390; https://doi.org/10.3390/v18030390 - 20 Mar 2026
Viewed by 760
Abstract
The immunosuppressive nature of porcine reproductive and respiratory syndrome virus (PRRSV) remains the central obstacle to its effective control. Conventional microRNA (miRNA)-based antiviral approaches are limited by their modest potency and the high risk of viral escape. Here, we rationally designed an engineered [...] Read more.
The immunosuppressive nature of porcine reproductive and respiratory syndrome virus (PRRSV) remains the central obstacle to its effective control. Conventional microRNA (miRNA)-based antiviral approaches are limited by their modest potency and the high risk of viral escape. Here, we rationally designed an engineered miRNA carrying a 5′-triphosphate (5′-PPP) terminus that integrates RIG-I-driven innate immune activation and sequence-specific gene silencing within a single molecule. In vitro-transcribed 5′-PPP miRNAs are efficiently recognized by the pattern-recognition receptor RIG-I, triggering a robust type I interferon response that counteracts PRRSV-induced immunosuppression. In MARC-145 cells, one such construct, 5′-PPP BZL-sRNA-20, potently inhibited PRRSV replication through the synergistic action of immune activation and gene silencing. However, in porcine alveolar macrophages (PAMs)—the natural host cells for PRRSV—the antiviral effect depended primarily on 5′-PPP-induced interferon responses, with the targeting sequence providing limited or context-dependent benefits. Dual-luciferase assays confirmed that the gene-silencing activity depends on 5′-PPP modification, which enhances the stability of BZL-sRNA-20. This bifunctional strategy establishes an “immune activation plus targeting” paradigm by simultaneously acting as a RIG-I ligand that triggers broad antiviral responses and specifically cleaves viral RNA via direct base-pairing to conserved regions of the PRRSV genome. These findings reveal the potential of engineered 5′-PPP miRNAs as immunomodulatory antiviral agents, while highlighting that the contribution of RNAi targeting varies depending on the cellular context. Full article
(This article belongs to the Section Animal Viruses)
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20 pages, 1737 KB  
Review
Mechanisms of APOBEC3 Packaging into HIV-1
by Mirriam Nzivo, Christoph G. W. Gertzen, Tom Luedde, Holger Gohlke and Carsten Münk
Viruses 2026, 18(3), 389; https://doi.org/10.3390/v18030389 - 20 Mar 2026
Viewed by 911
Abstract
Apolipoprotein B mRNA editing enzyme catalytic polypeptide 3s (APOBEC3s, A3s) are single-stranded DNA cytidine deaminases with antiviral activity against diverse DNA and RNA viruses. The human APOBEC3 locus encodes seven members: A3A, A3B, A3C, A3D, A3F, A3G, and A3H. Of these, A3C, A3D, [...] Read more.
Apolipoprotein B mRNA editing enzyme catalytic polypeptide 3s (APOBEC3s, A3s) are single-stranded DNA cytidine deaminases with antiviral activity against diverse DNA and RNA viruses. The human APOBEC3 locus encodes seven members: A3A, A3B, A3C, A3D, A3F, A3G, and A3H. Of these, A3C, A3D, A3F, A3G, and A3H are packaged into HIV-1, lacking the viral infectivity factor (VIF, HIV-1Δvif), while A3D, A3F, A3G, and A3H hap II exhibit strong antiviral activity. Packaging of A3s into virions is critical for viral restriction, yet the underlying mechanisms remain incompletely understood. A3 incorporation requires interactions with the GAG polyprotein, especially the matrix (MA) and nucleocapsid (NC) domains, and binding to cellular or viral RNAs. Specific amino acid residues within A3 proteins mediate these contacts, and A3G localization to lipid rafts facilitates packaging. While A3F and A3G incorporation have been extensively characterized, mechanisms for other A3s remain poorly defined. This review synthesizes current knowledge on A3 packaging, emphasizing the interplay of protein, RNA, and membrane determinants in efficient virion incorporation. Full article
(This article belongs to the Special Issue Host-Mediated Viral Mutations: APOBECs, ADARs, and Beyond)
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24 pages, 9277 KB  
Article
A STAT1-Knockout Mouse Model for Chapare Virus Infection and Pathogenesis
by Stephanie R. Monticelli, Ana I. Kuehne, Thomas G. Batchelor, Joshua B. Richardson, Zebulon Lapoint, Jennifer L. Williams, Susan R. Coyne, Jo Lynne W. Raymond, Xiankun Zeng, Christopher P. Stefan, Jeffrey W. Koehler, Jeffrey R. Kugelman and Andrew S. Herbert
Viruses 2026, 18(3), 388; https://doi.org/10.3390/v18030388 - 20 Mar 2026
Viewed by 816
Abstract
Chapare virus (CHAPV) is an Arenaviridae family member and causative agent of Chapare hemorrhagic fever (CHHF). Endemic to Bolivia, CHAPV was found to be the cause of several outbreaks of CHHF in Bolivia in 2003 and 2019 with high case-fatality rates and instances [...] Read more.
Chapare virus (CHAPV) is an Arenaviridae family member and causative agent of Chapare hemorrhagic fever (CHHF). Endemic to Bolivia, CHAPV was found to be the cause of several outbreaks of CHHF in Bolivia in 2003 and 2019 with high case-fatality rates and instances of human-to-human transmission. The pathogenesis of CHAPV infection is poorly understood, and no vaccines or antivirals are available, in part due to a dearth of available animal models. Mice lacking signal transducer and activator of transcription 1 (STAT1-/-) have been shown to succumb to infection by related arenaviruses, including Machupo virus, and were investigated for their susceptibility to CHAPV infection. Challenge with CHAPV resulted in partial lethality in STAT1-/- mice with a biphasic disease course characterized by initial viral load and pathology in the spleen and liver followed by inflammation and high viral titers in the brain and spinal cord that immediately preceded mortality. Adaptation in the brains of STAT1-/- mice resulted in a fully lethal mouse-adapted CHAPV variant, with a similar biphasic disease course, but virus in tissues was detected more proximal to challenge. The result of this study is a lethal small-animal rodent model for CHAPV that recapitulates many aspects of human CHAPV disease. Full article
(This article belongs to the Section Animal Viruses)
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11 pages, 448 KB  
Article
Medication Burden and Adherence of Antiretroviral Therapy Among Older People Living with HIV in the Context of Multimorbidity and Polypharmacy: A Multicenter Study
by Yaqin Zhou, Hong Zuo, Sitong Luo, Chunyuan Zheng and Honghong Wang
Viruses 2026, 18(3), 387; https://doi.org/10.3390/v18030387 - 20 Mar 2026
Viewed by 710
Abstract
Background: Population aging among people living with HIV (PLWH) has led to a growing burden of multimorbidity and complex medication regimens. However, the relationships between medication-related challenges and antiretroviral therapy (ART) adherence in older PLWH remain insufficiently understood. Methods: A multicenter cross-sectional study [...] Read more.
Background: Population aging among people living with HIV (PLWH) has led to a growing burden of multimorbidity and complex medication regimens. However, the relationships between medication-related challenges and antiretroviral therapy (ART) adherence in older PLWH remain insufficiently understood. Methods: A multicenter cross-sectional study was conducted among PLWH aged ≥50 years receiving routine HIV care in Hunan Province, China. Multimorbidity, polypharmacy, potential drug–drug interactions (PDDIs), medication-related burden, and ART adherence were assessed using validated instruments and clinical records. Path analysis was applied to examine hypothesized relationships based on the transactional model of stress and coping. Results: Among 301 participants, 54.2% experienced multimorbidity and 29.2% met criteria for polypharmacy. Medication-related burden was moderate to high. The proposed path model demonstrated good fit. Multimorbidity was positively associated with polypharmacy and PDDIs, both of which contributed to higher medication-related burden. Medication-related burden was the only factor directly associated with lower ART adherence, whereas polypharmacy and PDDIs showed no significant direct effects. Conclusions: Medication-related burden was significantly associated with both clinical complexity indicators and ART adherence among older PLWH. Interventions addressing patients’ subjective treatment burden may be critical for sustaining long-term adherence in aging HIV populations. Full article
(This article belongs to the Special Issue HIV in the Context of Chronic Disorders and Aging)
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33 pages, 811 KB  
Review
In Vitro and In Vivo Models for Drug Development Against Two Hemorrhagic Hareavirales: Rift Valley Fever and Crimean Congo Hemorrhagic Fever Viruses
by Sarah Chaput, Antoine Nougairède and Franck Touret
Viruses 2026, 18(3), 386; https://doi.org/10.3390/v18030386 - 19 Mar 2026
Viewed by 964
Abstract
Rift Valley fever virus (RVFV) and Crimean-Congo hemorrhagic fever virus (CCHFV) are designated by the World Health Organization as priority pathogens due to their epidemic potential, zoonotic transmission, and the absence of licensed therapeutics or vaccines. The development of effective antivirals critically relies [...] Read more.
Rift Valley fever virus (RVFV) and Crimean-Congo hemorrhagic fever virus (CCHFV) are designated by the World Health Organization as priority pathogens due to their epidemic potential, zoonotic transmission, and the absence of licensed therapeutics or vaccines. The development of effective antivirals critically relies on robust in vitro and in vivo models; however, progress is limited by the requirement for high-containment facilities. In this review, we provide a comprehensive overview of the experimental models currently available for RVFV and CCHFV, ranging from cell-based assays to animal models, and discuss their respective advantages, limitations, and translational relevance. We further highlight strategies allowing for BSL-2 experimentations, thereby expanding research accessibility, and accelerating the development of countermeasures against these high-priority pathogens. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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38 pages, 2616 KB  
Systematic Review
Wastewater as Sentinel for Emerging Viral Diseases in Livestock: A Systematic Review
by Mishuk Shaha, Ashutosh Das, Joyshri Saha, Md. Mizanur Rahaman, Mukta Das Gupta, Saranika Talukder and Subir Sarker
Viruses 2026, 18(3), 385; https://doi.org/10.3390/v18030385 - 19 Mar 2026
Viewed by 1229
Abstract
The accelerating frequency of emerging infectious diseases (EIDs) in livestock poses a significant threat to global food security, as well as to animal and public health. While wastewater-based surveillance (WBS) has advanced significantly for human health surveillance, its application to livestock production systems [...] Read more.
The accelerating frequency of emerging infectious diseases (EIDs) in livestock poses a significant threat to global food security, as well as to animal and public health. While wastewater-based surveillance (WBS) has advanced significantly for human health surveillance, its application to livestock production systems remains fragmented and lacks standardization. This review synthesizes current evidence on livestock wastewater-based surveillance (L-WBS) as an early-warning sentinel for emerging viral pathogens, evaluating their dynamics, economic impacts, biosecurity measures, and One Health implications. Existing studies demonstrate that L-WBS effectively detects emerging viral pathogens in agricultural effluent, swine manure, and municipal wastewater systems serving livestock regions, frequently preceding clinical outbreak recognition. We further conceptualized a multifactorial framework linking environmental drivers such as climate and ecological disruption and agricultural intensification to pathogen emergence dynamics. Economic assessments show substantial direct losses (approximately US$ 950 per H5N1-infected dairy cow and US$ 25.9 billion in African swine fever virus (ASFV)-related damages across China) alongside indirect costs from biosecurity implementation, workforce disruption, and supply-chain instability. We recommend prioritizing methodological standardization through unified sampling and extraction protocols, integration of next-generation sequencing for genomic surveillance, and cross-sectoral policy frameworks to operationalize L-WBS as a global early-warning infrastructure for mitigating zoonotic spillover and livestock-dependent community resilience. Full article
(This article belongs to the Section Animal Viruses)
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11 pages, 2266 KB  
Article
Establishment of a Cell-Fusing Agent Virus Infection Model in Aedes albopictus and Its Impact on Vector Competence for Zika Virus
by Dongqin Li, Ningxin Zhou, Li Xiong, Xi Pu, Mingqiang Li, Qing Liu, Lu Liu, Rui Xiao, Yuanhang Wang, Hengduan Zhang, Xiaoxia Guo, Dan Xing, Tongyan Zhao, Jiahong Wu and Yuting Jiang
Viruses 2026, 18(3), 384; https://doi.org/10.3390/v18030384 - 19 Mar 2026
Viewed by 683
Abstract
The overuse of chemical insecticides highlights the urgent need for novel vector control strategies. Insect-specific viruses (ISVs), such as the cell-fusing agent virus (CFAV), have shown potential to block arbovirus transmission by inhibiting viral replication in mosquitoes. However, the effects of CFAV beyond [...] Read more.
The overuse of chemical insecticides highlights the urgent need for novel vector control strategies. Insect-specific viruses (ISVs), such as the cell-fusing agent virus (CFAV), have shown potential to block arbovirus transmission by inhibiting viral replication in mosquitoes. However, the effects of CFAV beyond its natural host, Aedes aegypti, remain largely unexplored. In this study, we established a CFAV infection model in Aedes albopictus, a major vector for Zika virus (ZIKV), via intrathoracic injection. Stable infection was achieved, with viral loads reaching up to 107 copies per mosquito by day 10 post-injection. Nevertheless, high post-injection mortality (median survival: 3 days) was observed, which we attribute primarily to mechanical injury. No evidence of vertical transmission of CFAV was detected in Ae. albopictus. Co-injection of CFAV and ZIKV did not significantly affect ZIKV replication in this species. In contrast, in Ae. aegypti pre-infected with CFAV followed by oral ZIKV challenge, CFAV significantly reduced ZIKV infection rates in the ovaries at day 4 and viral loads in salivary glands at day 10. These findings demonstrate that while CFAV can productively infect Ae. albopictus, it does not undergo vertical transmission in this species, and has no inhibitory effect on ZIKV under the co-infection conditions tested. This study underscores challenges associated with using single ISVs such as CFAV for arbovirus control and highlights the complex, bidirectional role of multiple ISV co-infections. While exploring multi-ISV combinations may offer a potential strategy to enhance antiviral efficacy, their net effect—whether suppression or enhancement of arboviruses—warrants careful investigation. Full article
(This article belongs to the Section General Virology)
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11 pages, 246 KB  
Article
The Role of Immune Dysregulation Markers in Cardiovascular Risk of People Living with HIV: Association Among Intima Media Changes, CD4/CD8 Ratio, and CD4+ Cell Count Nadir
by Manuela Ceccarelli, Elena Delfina Ricci, Camilla Muccini, Laura Galli, Sergio Ferrara, Alessandra Tartaglia, Benedetto Maurizio Celesia, Elio Manzillo, Alessandra Guida, Giovanni Di Filippo, Rosa Basile, Antonella Castagna and Paolo Maggi
Viruses 2026, 18(3), 383; https://doi.org/10.3390/v18030383 - 18 Mar 2026
Viewed by 656
Abstract
HIV infection can promote persistent immune activation and endothelial dysfunction, contributing to atherosclerosis. Carotid intima–media thickness (cIMT) is an established marker of subclinical atherosclerosis. We evaluated the association between cIMT severity and two routinely available markers of immune dysregulation (CD4/CD8 ratio and nadir [...] Read more.
HIV infection can promote persistent immune activation and endothelial dysfunction, contributing to atherosclerosis. Carotid intima–media thickness (cIMT) is an established marker of subclinical atherosclerosis. We evaluated the association between cIMT severity and two routinely available markers of immune dysregulation (CD4/CD8 ratio and nadir CD4+ cell count) in people living with HIV (PLWH). We conducted an Italian multicenter cross-sectional study including 1148 PLWH who underwent carotid color Doppler ultrasound. We classified cIMT as ≤0.9, 1.0–1.4, or >1.4 mm and analyzed these categories using multinomial logistic regression, reporting adjusted odds ratios (aORs) with 95% confidence intervals (CIs). We adjusted models for age, sex, BMI, HIV acquisition risk factor, hypertension, diabetes, dyslipidemia/statin use, triglycerides, integrase inhibitor use, and ART duration. cIMT was ≤0.9 mm in 615 (53.6%) participants, 1.0–1.4 mm in 379 (33.0%), and >1.4 mm in 154 (13.4%). Using nadir CD4+ ≥ 200 cells/µL and CD4/CD8 ≥ 1.0 as reference, PLWH with nadir CD4+ < 200 and CD4/CD8 ≥ 1.0 had higher odds of cIMT 1.0–1.4 mm (aOR 1.66, 95% CI 1.02–2.69) and >1.4 mm (aOR 3.45, 95% CI 1.68–7.07). In conclusion, CD4+ nadir and this combined pattern were associated with greater cIMT severity, supporting a role for immune dysregulation in subclinical atherosclerosis. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
20 pages, 9633 KB  
Article
Pathological Characteristics of the Lung and Brain in Cotton Rats and BALB/c Mice Infected with Respiratory Syncytial Virus
by Ziou Wang, Bowei Jiang, Zhen Huang, Miao Liu, Zheli Li, Weihu Long, Hong Shen, Shengtao Fan, Yousong Ye and Zhangqiong Huang
Viruses 2026, 18(3), 382; https://doi.org/10.3390/v18030382 - 18 Mar 2026
Viewed by 670
Abstract
To compare the respiratory lesions and nervous system damage in cotton rats and BALB/c mice following respiratory syncytial virus (RSV) infection, and to evaluate their suitability as models for RSV-related respiratory and nervous system diseases, cotton rats and BALB/c mice were infected with [...] Read more.
To compare the respiratory lesions and nervous system damage in cotton rats and BALB/c mice following respiratory syncytial virus (RSV) infection, and to evaluate their suitability as models for RSV-related respiratory and nervous system diseases, cotton rats and BALB/c mice were infected with RSV via intranasal instillation, monitored daily for weight and temperature. At 3, 5, and 7 days post-infection (dpi), viral loads in the nasal turbinates, lungs, and brain tissues were quantified. Pathological changes and neuroinflammatory responses in the lungs and brain were assessed using hematoxylin and eosin (H&E) staining, Nissl staining, immunofluorescence, and Western blotting analysis, while the mRNA expression levels of inflammatory factors were specifically analyzed at 5 dpi. The results showed that viral loads in the nasal turbinates and lungs of cotton rats were significantly higher than those in BALB/c mice, accompanied by more extensive pulmonary inflammatory factor gene upregulation at 5 dpi and more pronounced lung histopathological alterations. In contrast, RSV RNA and antigens were detected in the brain tissues of BALB/c mice, at levels markedly lower than those in respiratory tissues, along with viral antigens primarily localized to the choroid plexus epithelium. No significant pathological or neuroinflammatory changes were observed in the brains of cotton rats at any examined time point. In conclusion, cotton rats provide advantages for modeling RSV-associated respiratory tract infection and pulmonary pathology, whereas under the experimental conditions of this study, BALB/c mice may be more appropriate for investigating RSV-associated CNS inflammatory responses, although the clinical relevance of these findings remains to be further validated. Full article
(This article belongs to the Section Animal Viruses)
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20 pages, 1393 KB  
Review
The Gene Encoding the Antisense Protein ASP of HIV-1: Origin, Distribution and Maintenance
by Myriam Abla Houmey, Sara Sadek, Coralie F. Daussy and Nathalie Chazal
Viruses 2026, 18(3), 381; https://doi.org/10.3390/v18030381 - 18 Mar 2026
Viewed by 817
Abstract
Human Immunodeficiency Virus Type 1 (HIV-1), the causative agent of the acquired immune deficiency syndrome (AIDS), originated from zoonotic transmissions of simian immunodeficiency viruses (SIVs) infecting African great apes, following complex cross-species transmission events and virus–host co-evolution. These processes were accompanied by multiple [...] Read more.
Human Immunodeficiency Virus Type 1 (HIV-1), the causative agent of the acquired immune deficiency syndrome (AIDS), originated from zoonotic transmissions of simian immunodeficiency viruses (SIVs) infecting African great apes, following complex cross-species transmission events and virus–host co-evolution. These processes were accompanied by multiple viral adaptations, particularly within structural and accessory genes, enabling evasion of host restriction factors and long-term viral persistence. In 1988, an antisense open reading frame (ORF) overlapping the env gene was proposed and subsequently confirmed by the identification of antisense transcripts and the antisense protein (ASP). An “intact” ASP ORF (defined as >150 codons) is predominantly conserved in pandemic HIV-1 group M viruses and shows evidence of positive selection, suggesting a selective advantage. Increasing evidence supports the hypothesis that the asp gene emerged de novo during the evolution of group M and contributed to viral adaptation and global spread in humans. This review combines a narrative review of the literature with original in silico analyses of HIV-1 and SIV sequences retrieved from the Los Alamos National Laboratory database. We systematically reassessed the distribution, length variability and conservation of the ASP ORF across HIV-1 groups (M, N, O, P), subtypes, circulating recombinant forms (CRFs), unique recombinant forms (URFs) and related SIV lineages. Our updated analyses confirmed the strong association between the presence of an “intact” ASP ORF and pandemic HIV-1 group M lineages, while revealing rare but notable antisense ORFs in selected SIVcpz and SIVgor strains. By integrating evolutionary, epidemiological and sequence-based evidence, we aim to clarify the origin and maintenance of the ASP ORF and to contextualize its emergence within the broader framework of overlapping gene evolution, de novo gene birth and the selective pressures shaping viral fitness and pandemic potential. Full article
(This article belongs to the Special Issue HIV-1 Infection and Immunometabolism: Relevance to HIV Pathogenesis and Persistence 3.0)
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18 pages, 1642 KB  
Article
Foundation Protein Language Models for Influenza A Virus T-Cell Epitope Prediction: A Transformer-Based Viroinformatics Framework
by Syed Nisar Hussain Bukhari and Kingsley A. Ogudo
Viruses 2026, 18(3), 380; https://doi.org/10.3390/v18030380 - 18 Mar 2026
Viewed by 844
Abstract
Influenza A virus remains a major cause of respiratory disease worldwide and poses a persistent challenge to vaccine development due to its rapid genetic evolution and antigenic variability. T-cell-based immunity has therefore gained increasing importance, as it can provide broader and more durable [...] Read more.
Influenza A virus remains a major cause of respiratory disease worldwide and poses a persistent challenge to vaccine development due to its rapid genetic evolution and antigenic variability. T-cell-based immunity has therefore gained increasing importance, as it can provide broader and more durable protection by targeting conserved viral regions. Accurate identification of T-cell epitopes (TCEs) is a fundamental requirement for epitope-based vaccine design and immunological research. Although numerous computational methods have been proposed, many existing approaches rely on handcrafted physicochemical features, which offer limited ability to capture contextual sequence dependencies. In this study, a transformer-based viroinformatics framework is proposed for the binary prediction of TCEs from Influenza A virus peptide sequences. The framework employs a pretrained Evolutionary Scale Modeling-2 (ESM-2) protein language model (PLM) to generate rich, contextualized embeddings directly from raw amino acid sequences, eliminating the need for manual feature engineering. These embeddings are processed using a lightweight attention-based transformer classifier to learn epitope-specific sequence patterns. The model achieves strong and stable predictive performance, attaining an accuracy of approximately 97% and an AUC close to 0.99 under stratified cross-validation. Ablation analysis further confirms that protein language model representations and self-attention contribute substantially to performance gains over classical machine learning baselines. To enhance practical reliability, Monte Carlo dropout is incorporated during inference to provide uncertainty-aware predictions, enabling differentiation between high-confidence and ambiguous peptide candidates. In addition, attention-based interpretability is used to identify residue-level contributions to model decisions, offering biologically meaningful insights into epitope recognition. Overall, this study demonstrates that PLMs combined with Transformer architectures provide an effective, interpretable, and a promising computational framework for Influenza A TCE discovery and vaccine research. Full article
(This article belongs to the Special Issue Viroinformatics and Viral Diseases)
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15 pages, 2655 KB  
Article
Post-Mortem Detection and Visualization of Mimivirus Reactivation in Fatal Viral Pneumonia
by Parandzem Khachatryan, Naira Karalyan, Anna Semerjyan, Marina Tatoyan, Hakob Davtyan, Arsham Yeremyan, Sona Hakobyan, Hranush Avagyan, Lina Hakobyan, Liana Abroyan, Aida Avetisyan, Elena Karalova, Nane Bayramyan, Tigranuhi Vardanyan, Vahagn Gevorgyan, Elina Arakelova, Alexandr Karalyan and Zaven Karalyan
Viruses 2026, 18(3), 379; https://doi.org/10.3390/v18030379 - 18 Mar 2026
Viewed by 946
Abstract
Mimivirus, a giant double-stranded DNA virus ($1.2$ Mbp), possesses unique bacteria-like features, including a Gram-positive staining reaction due to peptidoglycan-containing surface fibers. While detected in the respiratory secretions of pneumonia patients since 2005, its clinical role remains controversial due to high genetic variability [...] Read more.
Mimivirus, a giant double-stranded DNA virus ($1.2$ Mbp), possesses unique bacteria-like features, including a Gram-positive staining reaction due to peptidoglycan-containing surface fibers. While detected in the respiratory secretions of pneumonia patients since 2005, its clinical role remains controversial due to high genetic variability and detection challenges. This study aims to clarify the pathological significance of Mimivirus by investigating its presence and replication potential in human lung tissue, specifically exploring its association with fatal respiratory outcomes. A comparative post-mortem analysis was conducted on lung tissue samples from two cohorts: patients who succumbed to lethal viral pneumonia and a control group with no history of pulmonary pathology. Mimivirus is known to productively infect alveolar macrophages, suggesting they may serve as a reservoir for lung inflammation and tissue damage. Current evidence suggests it may act as an opportunistic or commensal agent, particularly in immunocompromised or critically ill patients. By systematically screening autopsy samples, this research seeks to establish whether Mimivirus is a primary causative agent of fatal pneumonia or an incidental inhabitant of the human respiratory tract. Full article
(This article belongs to the Special Issue Respiratory Viral Pathogenesis and Host-Microbe Crosstalk: From Bench to Bedside)
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15 pages, 588 KB  
Review
Genetic Diversity of the Polyomavirus JC and Implications for the Pathogenesis of Progressive Multifocal Leukoencephalopathy
by Michael P. Wilczek and Sebastien Lhomme
Viruses 2026, 18(3), 378; https://doi.org/10.3390/v18030378 - 18 Mar 2026
Viewed by 645
Abstract
JC Polyomavirus (JCPyV) is a non-enveloped virus with circular double stranded DNA responsible for the rare but fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). In its host, this virus exists in two different forms: one found in the periphery, named archetype, [...] Read more.
JC Polyomavirus (JCPyV) is a non-enveloped virus with circular double stranded DNA responsible for the rare but fatal demyelinating disease known as progressive multifocal leukoencephalopathy (PML). In its host, this virus exists in two different forms: one found in the periphery, named archetype, and another found in the central nervous system, named prototype. This form usually harbors recombinations in the non-coding control region (NCCR), a key region that contains sequences regulating viral replication and containing binding sites for cellular transcription factors. This form also contains mutations in the capsid protein, especially VP1. Due to the diversity of the JCPyV, a natural polymorphism also exists between the different genotypes. In this review, we aimed to summarize the main features of the archetype and prototype strains in order to facilitate the interpretation of sequence data that are increasingly generated by new sequencing technologies. This will also help to distinguish mutations associated with the natural polymorphism from those specific to the prototype form. Full article
(This article belongs to the Special Issue JC Polyomavirus)
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24 pages, 6873 KB  
Article
Characterisation of Naturally Occurring MERS-CoV Spike Mutations and Their Impact on Fusion and Neutralisation
by Rachael Dempsey, Hannah Goldswain, Joseph Newman, Nazia Thakur, Tracy MacGill, Todd Myers, Robert Orr, Dalan Bailey, James P. Stewart, Waleed Aljabr and Julian A. Hiscox
Viruses 2026, 18(3), 377; https://doi.org/10.3390/v18030377 - 18 Mar 2026
Viewed by 841
Abstract
In this study, the phenotypic consequences of naturally occurring single nucleotide polymorphisms (SNPs) in the Middle East respiratory syndrome coronavirus (MERS-CoV) Spike protein were investigated. The impact of Spike mutations on the syncytia formation and neutralisation of contemporary MERS-CoV strains is not currently [...] Read more.
In this study, the phenotypic consequences of naturally occurring single nucleotide polymorphisms (SNPs) in the Middle East respiratory syndrome coronavirus (MERS-CoV) Spike protein were investigated. The impact of Spike mutations on the syncytia formation and neutralisation of contemporary MERS-CoV strains is not currently well understood. Mutations were identified by aligning 584 MERS-CoV Spike sequences from either human clinical isolates collected between 2012 and 2024 or from a clinical isolate that had been passaged in human cells. Fifteen SNPs of interest occurring in the N-terminal domain (NTD), receptor binding domain (RBD) and adjacent to the S1/S2 cleavage site were selected for further characterisation based on their location in the Spike protein, frequency and identification in previous studies. A contemporary clade B, lineage 5 wildtype Spike sequence, obtained from a human MERS-CoV clinical isolate, was used as the backbone in this study. The mutations of interest were introduced to the wildtype backbone to generate Spike variants. Spike variants were characterised via cell–cell fusion assays, and a lentiviral pseudotyping system was used to investigate the impact of these Spike mutations on neutralisation. The I529T, E536K and L745F mutations were shown to increase fusion and syncytia formation. The L411F, T424I, L506F, L745F and T746K mutations were found to increase resistance to neutralisation by pooled patient sera. This study has identified novel naturally occurring Spike mutations that resulted in phenotypic differences in the syncytia formation and neutralisation of contemporary MERS-CoV strains. Continued investigation of the phenotypic consequences of MERS-CoV Spike mutations is essential for assessing the risk to public health, especially given the pandemic potential of this virus. Full article
(This article belongs to the Section Coronaviruses)
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24 pages, 1141 KB  
Review
Human Influenza Virus Infection: A Focus on Key Host Determinants Linked to Clinical Disease Severity
by Flora De Conto
Viruses 2026, 18(3), 376; https://doi.org/10.3390/v18030376 - 18 Mar 2026
Viewed by 1178
Abstract
Influenza viruses remain a major health threat, causing significant illness, death, and high healthcare costs worldwide, despite ongoing research and prevention efforts. A complex interaction between host and viral factors greatly influences the outcomes of influenza infection. Early research mainly focused on the [...] Read more.
Influenza viruses remain a major health threat, causing significant illness, death, and high healthcare costs worldwide, despite ongoing research and prevention efforts. A complex interaction between host and viral factors greatly influences the outcomes of influenza infection. Early research mainly focused on the influenza virus’s characteristics, but gaining an in-depth understanding of host factors involved in infection helps identify those that may influence disease severity. Notably, as the number of people with one or more comorbidities—that is, conditions that increase the risk of severe influenza—continues to rise, it becomes even more important to investigate the role of host factors. Recognizing host risk factors associated with severe outcomes, mainly caused by excessive inflammatory responses and disruption of epithelial barrier function, is crucial in identifying predictive markers and developing host-based prevention and treatment strategies, especially during pandemics. Moreover, early identification of host risk factors can help reduce severe outcomes and healthcare costs due to hospitalization. To achieve this, detailed analyses of the molecular signature of the host response to influenza virus infection are essential. This review highlights key host factors involved in severe influenza, allowing a better understanding of their roles, especially at the cellular level. Full article
(This article belongs to the Special Issue Interaction Between Influenza Virus and Host Cell)
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18 pages, 3670 KB  
Article
SFV Replicon Vector Harbouring Porcine Epidemic Diarrhoea Virus Immunogens Delivered by Attenuated Salmonella Typhimurium Induces PEDV Neutralising Antibodies and Lactogenic Immunogenicity in BALB/c Mice
by Chamith Hewawaduge, Ji-Young Park, Jaime C. Cabarles, Jr., Gayeon Won and John Hwa Lee
Viruses 2026, 18(3), 375; https://doi.org/10.3390/v18030375 - 17 Mar 2026
Viewed by 677
Abstract
Background: Porcine epidemic diarrhoea virus (PEDV) is a highly contagious pathogen causing severe diarrhoea and high mortality in neonatal piglets. Methods: In this study, consensus sequences encoding the N-terminal domain of spike subunit 1 (S1-NTD) and nucleocapsid (N) protein of PEDV were cloned [...] Read more.
Background: Porcine epidemic diarrhoea virus (PEDV) is a highly contagious pathogen causing severe diarrhoea and high mortality in neonatal piglets. Methods: In this study, consensus sequences encoding the N-terminal domain of spike subunit 1 (S1-NTD) and nucleocapsid (N) protein of PEDV were cloned into a eukaryotic expression vector pJHL204 and transformed into an attenuated Salmonella Typhimurium strain JOL2500. Antigen expression was confirmed by Western blot and immunofluorescence analyses. The recombinant strains were evaluated in vivo for safety, persistence, and immunogenicity. Immunogenicity was characterised by measuring antibody response, virus neutralising assays, cytokine profiling, and flow cytometric analysis of T cell subpopulation. Protective efficacy against salmonellosis in dams and passive transfer of neutralising antibodies to suckling mice were evaluated. Results: Vaccinated mice exhibited no adverse effects or bacterial persistence in major organs, confirming the vaccine’s safety. Immunisation elicited robust PEDV- and Salmonella-specific humoral and cell-mediated immune responses. Upon Salmonella challenge, vaccinated mice showed significantly reduced bacterial loads in splenic tissues. Furthermore, vaccinated dams and their offspring induced detectable anti-PEDV neutralising antibodies, indicating successful passive antibody transfer. Conclusion: Our findings indicate that the designed vaccine constructs provide a promising platform for inducing multifaceted immuno-protectivity against PEDV and salmonellosis. Full article
(This article belongs to the Special Issue Novel Insights into Porcine Viral Diseases: Recombinant Strains and Immune Responses)
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22 pages, 5476 KB  
Article
Genome-Wide RNAi Screening Identifies Novel Host Factors Involved in Influenza A Virus Infection in A549 Cells
by Qingchao Zhang, Lifang Zhang, Xinmeng Yang, Wei Wang, Xiliang Wang, Chengyu Jiang, Fengming Huang and Yanli Zhang
Viruses 2026, 18(3), 374; https://doi.org/10.3390/v18030374 - 17 Mar 2026
Viewed by 856
Abstract
Influenza A virus (IAV) remains a major global health threat, and host-directed antivirals may help overcome rapid viral mutation and drug resistance. Here, we performed a genome-wide siRNA screen in A549 cells using cell viability as an integrated endpoint to identify host determinants [...] Read more.
Influenza A virus (IAV) remains a major global health threat, and host-directed antivirals may help overcome rapid viral mutation and drug resistance. Here, we performed a genome-wide siRNA screen in A549 cells using cell viability as an integrated endpoint to identify host determinants of IAV (PR8/H1N1) infection. Using plate-normalized viability ratios, we identified 2134 genes with >40% viability change after infection (2048 UP and 86 DOWN; two-tailed t-test, n = 3; p < 0.05, FDR < 0.1). MetaCore pathway analysis showed enrichment of programs linked to host response and tissue injury control, including RAS-related signaling and multiple metabolic pathways such as estradiol, ubiquinone/mitochondrial redox, and benzo[a]pyrene/xenobiotic metabolism. DAVID Gene Ontology analysis further highlighted biological processes relevant to infection, including endocytosis, transcription, and translation, consistent with host pathways supporting viral replication. Benchmarking against meta-analyzed RNAi and CRISPR resources revealed that shared hits were enriched for translation, nucleocytoplasmic transport, and ER-Golgi trafficking, supporting external validity, whereas the large unique UP fraction was dominated by hormone metabolism, detoxification, and mitochondrial redox/CoQ pathways, consistent with viability-specific, tolerance-associated host response programs. Integrating the screen with DrugBank identified 174 druggable host genes corresponding to 345 candidate compounds. Together, these findings provide a systematic resource of host factors influencing H1N1 infection, improve understanding of influenza virus–host interactions, and offer a foundation for future development of host-directed antiviral strategies and drug repurposing efforts. Full article
(This article belongs to the Special Issue Advances in Understanding Viral Pathogenesis and Host Immune Responses to Arboviruses and Respiratory Viruses)
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5 pages, 436 KB  
Editorial
Beyond Pandemic Preparedness: Reframing Protracted War Against Infectious Diseases
by Ming Zheng
Viruses 2026, 18(3), 373; https://doi.org/10.3390/v18030373 - 17 Mar 2026
Viewed by 455
Abstract
Recent changes in the strategic language of the US National Institute of Allergy and Infectious Diseases (NIAID), including the removal of “biodefense” and “pandemic preparedness,” signal a substantive reordering of infectious-disease priorities [...] Full article
(This article belongs to the Special Issue The Interplay Between Viral Infections and Autoimmune Diseases)
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22 pages, 7761 KB  
Article
Analysis of SalHV-1 Genes by Structure Prediction and Comparison Shows an Expanded Core Gene Set of the Order Herpesvirales
by Richard J. Roller, Joan Martí-Carreras and Piet Maes
Viruses 2026, 18(3), 372; https://doi.org/10.3390/v18030372 - 17 Mar 2026
Viewed by 660
Abstract
The order Herpesvirales contains three families, Orthoherpesviridae, Alloherpesviridae, and Malacoherpesviridae. The time since divergence of families from the common ancestor makes protein primary sequence comparison an insensitive tool for identifying common genes. Comparison of three-dimensional protein structures can reveal similarities [...] Read more.
The order Herpesvirales contains three families, Orthoherpesviridae, Alloherpesviridae, and Malacoherpesviridae. The time since divergence of families from the common ancestor makes protein primary sequence comparison an insensitive tool for identifying common genes. Comparison of three-dimensional protein structures can reveal similarities that are not evident in primary sequences. Salmonid herpesvirus 1 (SalHV-1) is an alloherpesvirus. Complete sequencing of SalHV-1 VR-868 strain Winthrop by a combination of short- and long-read methods revealed 120 putative open reading frames (ORFs). BLAST search for similar protein sequences discovered five ORFs that encoded proteins with homologs in the orthoherpesviruses, including the major capsid protein, capsid triplex subunit 2, the catalytic subunit of the DNA polymerase, the helicase subunit of the helicase/primase complex, and the terminase ATPase subunit. An annotation of the ORFs of SalHV-1 was performed in which ORFs of SalHV-1 were modeled using AlphaFold3, and the models were used as prompts for structural similarity search using DALI and FoldSeek. Completion of this search strategy for the entire genome expanded the set of genes shared among the Herpesvirales to include additional proteins related to DNA replication and genome integrity, capsid assembly and genome packaging, and capsid nuclear egress. No homologs for any tegument proteins or proteins of the conserved entry apparatus of the Herpesviridae (gB, gH or gL) were discovered. Full article
(This article belongs to the Section Animal Viruses)
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15 pages, 1873 KB  
Case Report
First Detection of Usutu Virus in Harbor Seals (Phoca vitulina)
by Anne Schwarzer, Franziska Schopf, Insa Dammann, Katharina Kramer, Tanja Rosenberger, Christine Fast, Michaela Geese, Martin H. Groschup, Balal Sadeghi and Ute Ziegler
Viruses 2026, 18(3), 371; https://doi.org/10.3390/v18030371 - 17 Mar 2026
Viewed by 1051
Abstract
The zoonotic Orthoflavivirus Usutu virus (USUV) is distributed throughout Germany, putting hosts at a considerable risk of infection nationwide. Besides birds as reservoir hosts, a broad range of accidental hosts is suspected. However, there are few reports documenting the progression of USUV-associated disease. [...] Read more.
The zoonotic Orthoflavivirus Usutu virus (USUV) is distributed throughout Germany, putting hosts at a considerable risk of infection nationwide. Besides birds as reservoir hosts, a broad range of accidental hosts is suspected. However, there are few reports documenting the progression of USUV-associated disease. This case report describes the course of fatal USUV infections in three harbor seals (Phoca vitulina) from a rescue center on the North Sea coast in Germany. Corresponding samples were analyzed using (histo-)pathological, immunohistochemical, molecular and phylogenetic methods. The most prevalent findings in clinically affected animals were neurological signs and non-suppurative encephalitis. All animals were found dead or had been euthanized due to animal welfare reasons within 30 h after the onset of clinical signs. Blood samples taken from another 37 young harbor seals from the same rescue center in the same year revealed two further asymptomatic USUV RNA and antibody-positive animals. The sequences were found to belong to USUV lineages Europe 2 and Africa 3, which are known to circulate in birds in Germany. This case report highlights the importance of USUV as a potential diagnosis for neurological impairments in marine mammals and documents the first cases of USUV infection in harbor seals. Full article
(This article belongs to the Special Issue Pathogenesis and Persistence in Flavivirus Infections: Mechanisms, Biomarkers, and Clinical Implications)
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15 pages, 2056 KB  
Article
Viral Escape from a Candidate HIV-1 Vaccine Targeting Protease Cleavage Sites Is Associated with a Dramatic Fitness Loss in SIVmac239-Infected Cynomolgus Macaques
by So-Yon Lim, Ma Luo and James B. Whitney
Viruses 2026, 18(3), 370; https://doi.org/10.3390/v18030370 - 17 Mar 2026
Viewed by 665
Abstract
A novel HIV-1 vaccine candidate under development targeting the highly conserved protease cleavage regions reduced viral acquisition and delayed disease progression in a macaque SIV-challenge model. Breakthrough virus isolated from vaccinees and control animals were sequenced in the regions surrounding the SIV protease [...] Read more.
A novel HIV-1 vaccine candidate under development targeting the highly conserved protease cleavage regions reduced viral acquisition and delayed disease progression in a macaque SIV-challenge model. Breakthrough virus isolated from vaccinees and control animals were sequenced in the regions surrounding the SIV protease cleavages. We identified unique viral mutations that were associated with alterations in viral load and maintenance of CD4+ T cell counts in vaccinees. To evaluate whether the vaccine-elicited mutations were detrimental to virus fitness, we produced 11 mutant constructs and transfection-derived viral stocks harboring mutations in both PCS2 (in CA/p2) and PCS12 (in Nef) that had emerged at high frequency during breakthrough viremia. Virus preparations harboring mutations displayed impaired proteolytic Gag processing, reduced viral RNA incorporation and p27-CA content. These mutants were also compromised in their ability to replicate in primary cells and cell lines. Interestingly, we observed only partial compensation of these PCS2 defects by downstream mutation at PCS12. In sum, we demonstrate that vaccine-elicited immunity directed to viral protease cleavage regions impair viral escape, and breakthrough virus cannot easily restore replicative fitness. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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Article
A History of Methamphetamine Use Disorder in People with HIV Is Associated with Altered Functional Response to Risky Choice
by Joseph P. Happer, Susan F. Tapert, Igor Grant, Amanda Bischoff-Grethe and on behalf of the Translational Methamphetamine AIDS Research Center (TMARC) Group
Viruses 2026, 18(3), 369; https://doi.org/10.3390/v18030369 - 17 Mar 2026
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Abstract
Methamphetamine (METH) use is highly prevalent among people with HIV (PWH) and those at risk and may contribute to overall worse health outcomes. Poorer health-related problems may be mediated by METH enhancing risky decision-making among PWH. While both METH and HIV are known [...] Read more.
Methamphetamine (METH) use is highly prevalent among people with HIV (PWH) and those at risk and may contribute to overall worse health outcomes. Poorer health-related problems may be mediated by METH enhancing risky decision-making among PWH. While both METH and HIV are known to have overlapping and deleterious effects on the frontostriatal neural circuitry essential for decision-making, few studies have examined their combined effects. Eighty-eight participants stratified by HIV and a history of METH use disorder completed a risky decision-making paradigm, which involved choosing among safe (20¢) and risky (40¢/80¢ win or loss) choices, during blood-oxygen level-dependent functional magnetic resonance imaging (fMRI). Linear mixed-effects models were used to assess voxelwise differences in group and choice constrained to the anterior cingulate cortex (ACC), insula, and striatum. Despite similar choice behavior across groups, PWH and a history of METH use disorder had greater activation of the ACC and caudate than either condition alone (i.e., HIV+/METH− and HIV−/METH+), which was similar to seronegative, non-using controls. Within the ACC in particular, these differences may have been driven by safe choices. A longer estimated duration of HIV infection was associated with greater ACC activation to risky choices for PWH regardless of METH use history. These findings suggest that PWH and a history of METH use disorder may exhibit compensatory activation of regions associated with decision-making in the context of rewards and that the effects of HIV and past METH use might not be additive. Full article
(This article belongs to the Special Issue HIV and Drugs of Abuse, 4th Edition)
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