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Viruses, Volume 18, Issue 1 (January 2026) – 149 articles

Cover Story (view full-size image): Several MaAv can cause severe, often fatal hemorrhagic fevers in humans following zoonotic transmissions. Lassa and Junín viruses remain major regional public health threats, while the globally distributed lymphocytic choriomeningitis virus is an underappreciated human pathogen of clinical significance. Despite this burden, no MaAv FDA-approved vaccines or antivirals exist. We screened the Pandemic Response Box and identified three potent inhibitors of MaAv replication: the Tat protein antagonist Ro-24-7429, a pirolazamide-based DHODH inhibitor, and verdinexor, a selective inhibitor of nuclear export targeting XPO1/CRM1. Notably, verdinexor displayed striking antiviral synergy in combination with Ro-24-7429 or the picolinamide-based DHODH inhibitor. Our findings highlight host-directed nuclear export inhibition as a promising strategy for combination therapy against pathogenic MaAv. View this paper
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14 pages, 2341 KB  
Article
Reversible Effects of Integrase Inhibitors on Newly Differentiated Adipocytes
by Richard Taylor Pickering, Archana Asundi, Alex Olson, Katie Soden and Nina H. Lin
Viruses 2026, 18(1), 149; https://doi.org/10.3390/v18010149 - 22 Jan 2026
Viewed by 281
Abstract
Weight gain has been associated with integrase strand transfer inhibitors (INSTIs) in real-world studies; however, the causality of this relationship is unclear. Thus, we examined the effects of the INSTI, Dolutegravir (DTG), on human adipose cells in vitro and the reversibility of these [...] Read more.
Weight gain has been associated with integrase strand transfer inhibitors (INSTIs) in real-world studies; however, the causality of this relationship is unclear. Thus, we examined the effects of the INSTI, Dolutegravir (DTG), on human adipose cells in vitro and the reversibility of these effects by switching to a protease inhibitor, Darunavir (DRV). We established cultures of human adipose stem cells (ASCs) and newly differentiated adipocytes from individuals without HIV. For adipocytes, cells were exposed to DTG or DRV for 7 days, after which cells were maintained or switched to another ART. Experiments examining ASCs and the effects on adipogenesis initiated exposure during proliferation and continued throughout differentiation. Adipogenic outcomes included triglyceride content, gene expression, and adipokine secretion. Metabolic outcomes included lactate production, lipolysis, and oxygen consumption rates. DTG suppressed the secretion of adiponectin and leptin, and this was reversed following the switch to DRV in adipocytes without the altered expression of adipogenic genes. DTG exposure increased markers of endoplasmic reticulum stress, elevated lactate production, and suppressed oxygen consumption in ASCs. Exposure to DTG during differentiation lowered triglyceride accumulation and adiponectin secretion without altering the expression of adipogenic markers. Thus, DTG exposure resulted in changes in adipocyte function consistent with the progression of metabolically adverse phenotypes, and these effects were reversible. Full article
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6 pages, 735 KB  
Article
Viruses Infecting Cuban Honey Bees and Evolution of Deformed-Wing-Virus Variants
by Poppy J. Hesketh-Best, Anais R. Luis, Declan C. Schroeder and Stephen J. Martin
Viruses 2026, 18(1), 148; https://doi.org/10.3390/v18010148 - 22 Jan 2026
Viewed by 232
Abstract
Cuba is in a unique situation in which it has a large (220,000 managed colonies) and isolated honey bee population due to a 60+ year ban on the importation of bees. Despite this, the ectoparasitic mite Varroa destructor arrived in 1996, and with [...] Read more.
Cuba is in a unique situation in which it has a large (220,000 managed colonies) and isolated honey bee population due to a 60+ year ban on the importation of bees. Despite this, the ectoparasitic mite Varroa destructor arrived in 1996, and with it came deformed wing virus (DWV). In 2018, an island-wide survey detected varroa and DWV in 91% of colonies. In this study, we conducted a full-virome analysis on some of these samples, along with additional samples collected in 2021. For the first time, we detected two variants of Lake Sinai Virus and confirmed the absence of the normally widespread black queen cell virus in Cuba. We also detected both DWV-A and DWV-B master variants, with DWV-B being the dominant variant. Interestingly, the DWV-B/A recombinant was also detected, indicating that despite Cuba’s isolated nature, the pattern of DWV evolution mirrors that found in the USA and Europe. However, this pattern is not found in neighboring Latin America, China, or Japan, where the DWV-A master variant continues to be dominant. How and why two distinct evolutionary DWV pathways have arisen remain a mystery. Full article
(This article belongs to the Special Issue Advances in Honey Bee Viruses Research)
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9 pages, 717 KB  
Communication
HIV-1 Genetic Diversity and Drug Resistance Mutation Profiles in Donetsk, Luhansk and Zaporizhzhia Regions
by Anastasiia Antonova, Anatolii Vinokurov, Daria Kustova, Andrei Pochtovyi, Daria Ogarkova, Anna Kuznetsova, Ruslan Adgamov, Elena Tsyganova, Inna Kulikova, Andrei Plutnitskii, Aleksandr Gintsburg, Vladimir Gushchin and Aleksei Mazus
Viruses 2026, 18(1), 147; https://doi.org/10.3390/v18010147 - 22 Jan 2026
Viewed by 396
Abstract
The first major HIV outbreak in the Eastern Europe and Central Asia (EECA) region was registered. Phylogeographic analysis revealed that the main exporters of the virus were Donetsk and Lugansk, from which most migration events occurred, and the predominant genetic variant in Donetsk [...] Read more.
The first major HIV outbreak in the Eastern Europe and Central Asia (EECA) region was registered. Phylogeographic analysis revealed that the main exporters of the virus were Donetsk and Lugansk, from which most migration events occurred, and the predominant genetic variant in Donetsk was subtype A. However, despite a relatively high level of understanding of HIV genetic diversity, data on resistance mutations remain limited. The aim of this study is to assess HIV genetic diversity and drug resistance in Donetsk, Luhansk and Zaporizhzhia regions. A comprehensive examination was conducted, encompassing 392 sequences covering the integrase-coding region of the HIV-1 pol gene. Subtyping was achieved through various programs, including COMET, the Stanford Database, BLAST and REGA. The study also involved phylogenetic analysis to clarify HIV genovariants. The profiles and levels of drug resistance were determined. The overall prevalence of drug resistance mutations to the integrase strand transfer inhibitors (INSTIs) among the studied patients was 3.6% (95% CI, 1.7–5.4%). The most commonly detected major DRMs for INSTIs were G140R (4, 28.6%) and Y143R (3, 21.4%), followed by R263K (2, 14.3%), G140RG (2, 14.3%), Y143YS (2, 14.3%), Y143YC (1, 7.1%) and Q148QR (1, 7.1%). A high-level resistance was observed for RAL—8/14 (57.1%), CAB—6/14 (42.9%) and EVG—2/14 (14.3%). The results presented are part of a further larger study and are preliminary. The results of this study suggest a moderate HIV-1 resistance situation in the Donetsk, Luhansk and Zaporizhzhia regions, but require further monitoring. Full article
(This article belongs to the Section General Virology)
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20 pages, 2879 KB  
Article
Three Staphylococcus Bacteriophages Isolated from Swine Farm Environment in Quebec, Canada, Infecting S. chromogenes
by Mousumi Sarker Chhanda, Rébecca E. St-Laurent, Valérie E. Paquet, Nicolas Deslauriers, Cynthia Gagné-Thivierge, Martine Denicourt, Marie-Ève Lambert, Antony T. Vincent and Steve J. Charette
Viruses 2026, 18(1), 146; https://doi.org/10.3390/v18010146 - 22 Jan 2026
Viewed by 245
Abstract
Exudative epidermitis (EE), caused by Staphylococcus hyicus, represents an issue for swine production, particularly due to antimicrobial resistance. In this project, we isolated bacteriophages using S. hyicus as host and studied them as a potential alternative to antibiotic treatment in Quebec, Canada. [...] Read more.
Exudative epidermitis (EE), caused by Staphylococcus hyicus, represents an issue for swine production, particularly due to antimicrobial resistance. In this project, we isolated bacteriophages using S. hyicus as host and studied them as a potential alternative to antibiotic treatment in Quebec, Canada. Three phages, STAE-4, STAF-3, and STAM-1, were isolated from swine farm samples using a single S. hyicus strain (SC366) as the host. Transmission electron microscopy revealed that all three phages exhibited a siphovirus-like morphology, and RAPD-PCR profiling indicated that the phages were genetically distinct. Whole genome sequencing confirmed these differences and showed that the three phages were closely related to each other, and, more importantly, highly similar to phages previously described as infecting Staphylococcus chromogenes, a species closely related to S. hyicus. Host range analysis confirmed that the three phages preferentially infected the S. chromogenes strains included in the study, exhibiting minimal to no lytic activity against other strains of S. hyicus or Staphylococcus agnetis, another closely related species. The only exception was the host S. hyicus strain SC366, which was effectively infected by all three phages, albeit less efficiently than the most sensitive S. chromogenes strain (SC385). Adsorption tests further supported these observations, showing that phages bound to strain SC366 much more quickly than to SC385, despite the lower lytic activity observed. Taken together, these results highlight that while the phages retain some capacity to infect S. hyicus, their biological properties point to a stronger adaptation to S. chromogenes, indicating that they are not suitable candidates for controlling EE. Full article
(This article belongs to the Section Bacterial Viruses)
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29 pages, 7326 KB  
Article
Virion-Independent Extracellular Vesicle (EV)-Dependent Transmission of SARS-CoV-2 as a Potential New Mechanism of Viral RNA Spread in Human Cells
by Nergiz Ekmen, Ali Riza Koksal, Dong Lin, Di Tian, Paul Thevenot, Sarah Glover and Srikanta Dash
Viruses 2026, 18(1), 145; https://doi.org/10.3390/v18010145 - 22 Jan 2026
Viewed by 359
Abstract
The concentration of extracellular vesicles (EVs) in the peripheral blood of COVID-19 patients is increased. Nevertheless, their potential role in the transmission of infection remains unclear. This study was performed to determine whether EVs produced by the sub-genomic replicon system developed in Baby [...] Read more.
The concentration of extracellular vesicles (EVs) in the peripheral blood of COVID-19 patients is increased. Nevertheless, their potential role in the transmission of infection remains unclear. This study was performed to determine whether EVs produced by the sub-genomic replicon system developed in Baby Hamster Kidney (BHK-21) cells could transfer SARS-CoV-2 replicon RNA, leading to the establishment of a viral replication system in human cells. Purified EVs from the SARS-CoV-2 sub-genomic replicon cell line BHK-21 were cultured with a naive human cell line. The success of EV-mediated transfer of SARS-CoV-2 replicon RNA and its productive replication was assessed using G-418 selection, a luciferase assay, immunostaining, and Western blot. We found that the A549 cell line cultured with EVs isolated from SARS-CoV-2 BHK-21 replicon cells developed G-418-resistant cell colonies. SARS-COV-2 RNA replication in A549 cells was confirmed by nano luciferase, Nsp1 protein. SARS-CoV-2 RNA replication causes massive morphological changes. Treatment of cells with the FDA-approved Paxlovid demonstrated a dose-dependent inhibition of viral replication. We isolated two human epithelial cell lines (gastrointestinal and neuroblastoma) and one vascular endothelial cell line that stably support high-level replication of SARS-CoV-2 sub-genomic RNA. Viral elimination did not revert the abnormal cellular shape, vesicle accumulation, syncytia formation, or EV release. Our study’s findings highlight the potential implications of EV-mediated transfer of replicon RNA to permissive cells. The replicon model is a valuable tool for studying virus-induced reversible and irreversible cellular reprogramming, as well as for testing novel therapeutic strategies for SARS-CoV-2. Full article
(This article belongs to the Section Coronaviruses)
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16 pages, 10086 KB  
Article
Kaposi Sarcoma: Retrospective Clinical Analysis with a Focus on Age and HIV Serostatus
by Zuhal Erçin and Mehtap Toprak
Viruses 2026, 18(1), 144; https://doi.org/10.3390/v18010144 - 22 Jan 2026
Viewed by 210
Abstract
Studying the incidence of Kaposi sarcoma in relation to key variables can guide targeted research and subtype-specific clinical interventions. We reviewed the records of all patients who visited our hospital’s dermatology outpatient clinic, and patients who were clinically and histopathologically diagnosed with Kaposi [...] Read more.
Studying the incidence of Kaposi sarcoma in relation to key variables can guide targeted research and subtype-specific clinical interventions. We reviewed the records of all patients who visited our hospital’s dermatology outpatient clinic, and patients who were clinically and histopathologically diagnosed with Kaposi sarcoma were included in the study. The age, gender, lesion location, anti-HIV test results, and comorbidities of the patients were recorded. Thirty-three patients with Kaposi sarcoma were identified. The male/female ratio was 2.7:1. The Kaposi sarcoma lesions were statistically significantly more prevalent in the lower extremities of HIV-negative patients (p = 0.005). Receiver operating characteristic (ROC) curve analysis identified 59 years as the optimal age cutoff for distinguishing between HIV-positive and HIV-negative patients. Anti-HIV positivity was significantly higher in individuals aged 59 and younger compared to those aged 60 and older (p < 0.001). To the best of our knowledge, this is the first study to demonstrate a statistically significant higher prevalence of lower extremity lesions among HIV-negative patients and to identify 59 years as the optimal age cutoff for distinguishing between HIV-positive and HIV-negative Kaposi sarcoma patients using ROC curve analysis. The age-related patterns observed in this study warrant further investigation. Full article
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21 pages, 2810 KB  
Article
Improved Safety of New MicroRNA-Regulated Oncolytic Coxsackievirus B3 Observed After Intravenous Administration in Colorectal-Tumor-Bearing Mice
by Leslie Elsner, Luisa Hinze, Ahmet Hazini, Lisanne Heimann, Anja Geisler, Babette Dieringer, Karin Klingel, Sophie Van Linthout, Jens Kurreck, Robert Klopfleisch and Henry Fechner
Viruses 2026, 18(1), 143; https://doi.org/10.3390/v18010143 - 22 Jan 2026
Viewed by 250
Abstract
Oncolytic coxsackievirus B3 (oCVB3) strain PD-H has shown potent oncolytic efficacy and a remarkable safety profile in the treatment of colorectal cancer in vivo after intratumoral (i.t.) injection. In this study, we investigated the safety and efficiency of PD-H following intravenous (i.v.) virus [...] Read more.
Oncolytic coxsackievirus B3 (oCVB3) strain PD-H has shown potent oncolytic efficacy and a remarkable safety profile in the treatment of colorectal cancer in vivo after intratumoral (i.t.) injection. In this study, we investigated the safety and efficiency of PD-H following intravenous (i.v.) virus administration. When injected i.v. into Balb/C mice bearing subcutaneous Colon-26 tumors, PD-H led to slightly reduced tumor progression and a significant increase in animal survival, but it also caused multi-organ infection and tissue damage. To improve the safety profile of PD-H, we inserted microRNA target sites (miR-TS) of the heart-specific miR-1, pancreas-specific miR-375, liver-specific miR-122, and brain-specific miR-124 or the tumor-suppressor miR-145 into the genome of PD-H and generated the viruses PD-622TS and PD-145TS. Both viruses replicated similarly and induced cytotoxicity comparable to that of PD-H in the colorectal carcinoma cell lines Colon-26 and CT-26Luc. Their replication was inhibited in HEK293T cells transiently transfected with the cognate microRNAs. In vivo, i.v. administration of PD-145TS and PD-622TS to healthy Balb/C mouse resulted in significantly lower viral titers in the organs of mice and led to significantly less-intense pathological alterations compared to PD-H. PD-622TS injected i.v. into Balb/C mice with CT-26Luc-induced peritoneal carcinomatosis did not induce off-target alterations in normal organs, but it failed to induce a therapeutic effect. These data indicate that PD-H or microRNA-regulated PD derivatives exhibit only limited therapeutic efficacy following i.v. injection in colorectal tumor-bearing mice. However, the newly engineered microRNA-regulated PD-H variants demonstrate improved safety profiles. Full article
(This article belongs to the Special Issue Oncolytic Virus Engineering for Tumor Immunotherapy)
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10 pages, 347 KB  
Article
The Role of Prior HBV Infection on the Efficacy of 3TC/DTG as a Maintenance Therapy
by Tommaso Matucci, Sara Occhineri, Alessandra Palomba, Maria Linda Vatteroni, Laura Del Bono, Marina Polidori, Riccardo Iapoce, Alberto Borghetti and Marco Falcone
Viruses 2026, 18(1), 142; https://doi.org/10.3390/v18010142 - 22 Jan 2026
Viewed by 207
Abstract
Lamivudine/dolutegravir (3TC/DTG) is an effective and well-tolerated antiretroviral regimen for most people with HIV (PWH) who are virologically suppressed; however, specific clinical characteristics, such as prior hepatitis B virus (HBV) exposure or archived resistance-associated mutations (RAMs), may influence the risk of virological failure [...] Read more.
Lamivudine/dolutegravir (3TC/DTG) is an effective and well-tolerated antiretroviral regimen for most people with HIV (PWH) who are virologically suppressed; however, specific clinical characteristics, such as prior hepatitis B virus (HBV) exposure or archived resistance-associated mutations (RAMs), may influence the risk of virological failure (VF). We conducted a retrospective, monocentric cohort study to evaluate the incidence and predictors of VF among PWH who switched to 3TC/DTG after achieving virological suppression (HIV-RNA < 50 copies/mL). A total of 188 PWH were included. Over 5082 patient-years of follow-up (PYFU), 8 individuals (4.3%) experienced VF, corresponding to an incidence rate of 1.45 per 1000 PYFU. The cumulative probabilities of VF at 1, 2, 3, 4, and 5 years were 0.6%, 2.7%, 2.7%, 4.2%, and 22.3%, respectively. In exploratory multivariable analyses, anti-HBc positivity was associated with an increased risk of VF (adjusted hazard ratio [aHR] 4.80, 95% CI 1.03–22.43; p = 0.046). After adjustment for age and sex, individuals with anti-HBc positivity who had switched from a tenofovir-containing regimen showed the highest risk of VF compared with anti-HBc-negative individuals without prior tenofovir exposure (aHR 15.06, 95% CI 1.40–161.38; p = 0.025). Given the limited number of virological events, these findings should be interpreted with caution. Nevertheless, they suggest that prior HBV exposure, particularly in the context of tenofovir discontinuation, may represent a clinically relevant factor when considering simplification to 3TC/DTG. Full article
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11 pages, 2041 KB  
Communication
Virome Analysis of Lemon Plants with Vein Clearing Symptoms Reveals Mixed Infection of Citrus Vein Clearing Virus, Iris Domestica Betaflexivirus 1 and Hop Stunt Viroid
by Myeonghwan Kwak, Eui-Joon Kil, Angelo De Stradis and Giuseppe Parrella
Viruses 2026, 18(1), 141; https://doi.org/10.3390/v18010141 - 22 Jan 2026
Viewed by 167
Abstract
Citrus yellow vein clearing virus (CYVCV) is the causative agent of the yellow vein clearing disease (YVCD), a worldwide and highly destructive disease in lemon (Citrus lemon) and sour orange trees (C. aurantium). The typical symptoms of vein clearing [...] Read more.
Citrus yellow vein clearing virus (CYVCV) is the causative agent of the yellow vein clearing disease (YVCD), a worldwide and highly destructive disease in lemon (Citrus lemon) and sour orange trees (C. aurantium). The typical symptoms of vein clearing are believed to be associated with CYVCV infection in citrus, so virus-specific diagnostic systems are currently used to confirm infection. In the present study, virome analysis based on high-throughput sequencing (HTS) on a lemon plant showing YVCD revealed mixed infection of CYVCV, iris domestica betaflexyviridae 1 (IDBV), and hop stunt viroid (HSVd). This multiple infection was confirmed in other two lemon plants with similar symptoms using virus/viroid specific primers. This is the first report of IDBV in lemon. Through molecular characterization and the reconstruction of phylogenetic relationships, a possible origin of the viruses/viroid identified in lemon has been hypothesized. Such mixed infections raise new questions about their role in the expression of YVCD symptoms observed on lemon. Full article
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27 pages, 1016 KB  
Review
The Differentially Regulated Cousins: Insights into the Differences in Transcriptional Regulatory Mechanisms Between HTLV-1 and HIV-1
by Omnia Reda and Yorifumi Satou
Viruses 2026, 18(1), 140; https://doi.org/10.3390/v18010140 - 22 Jan 2026
Viewed by 606
Abstract
HTLV-1 and HIV-1 represent biologically significant, structurally close, and equally problematic yet divergent human retroviruses. Although both infect CD4+ T cells and share similar structural elements, they differ markedly in genomic stability, transmission dynamics, clinical progression, and, most importantly, their transcriptional regulatory mechanisms. [...] Read more.
HTLV-1 and HIV-1 represent biologically significant, structurally close, and equally problematic yet divergent human retroviruses. Although both infect CD4+ T cells and share similar structural elements, they differ markedly in genomic stability, transmission dynamics, clinical progression, and, most importantly, their transcriptional regulatory mechanisms. HTLV-1, an ancient virus with a limited global burden, often remains asymptomatic for decades before potentially causing ATL or HAM/TSP. Conversely, HIV-1, a relatively recent zoonotic transmission, undergoes rapid replication, exhibits high genetic diversity, and causes progressive immunodeficiency unless controlled by antiretroviral therapy (ART). At the molecular level, HTLV-1 maintains proviral latency through a balanced bidirectional transcription of regulatory genes (e.g., Tax and HBZ) that manipulate host transcription and immune evasion pathways, facilitating persistence and oncogenesis. HBZ and Tax were shown to contribute to driving the progressive acquisition of Treg-like and HLA class II phenotype in chronically activated CD4+ T-cells, promoting tolerogenic antigen presentation and immune evasion in ATL cells. This well-controlled differential expression of HTLV-1 regulatory genes is attributed to multiple intragenic virus regulatory mechanisms, which will be discussed in this review. In contrast, HIV-1 transcription is driven by a tightly regulated 5′ LTR promoter involving host factors such as NF-κB, Sp1, AP-1, and NFAT, among others, with strong influence imposed by the landscape of the provirus integration site, playing a pivotal role in latency and reactivation. The distinct regulatory circuitry of each virus suggests a key difference in their essential regulation, with HTLV-1 primarily relying on intragenic mechanisms, while HIV-1 relies more heavily on interactions with the surrounding host environment to control its expression. This difference underscores unique therapeutic challenges in managing viral latency, persistence, and pathogenesis. Full article
(This article belongs to the Special Issue Unraveling the Pathogenesis of Persistent Virus Infection)
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10 pages, 214 KB  
Article
Evaluating the Clinical Impact of BioFire Spotfire R/ST on the Management of Pediatric Respiratory Presentations in the Emergency Department: A Pre–Post Cross-Sectional Study in Chile
by Dona Benadof, Mirta Acuña, Yennybeth Leiva and Daniel Conei
Viruses 2026, 18(1), 139; https://doi.org/10.3390/v18010139 - 22 Jan 2026
Viewed by 231
Abstract
Respiratory infections represent one of the leading causes of pediatric consultations and hospitalizations in Chile, where rapid etiological identification is essential for clinical decision-making. We evaluated the impact of implementing the BIOFIRE® SPOTFIRE® Respiratory (R) Panel in the pediatric Emergency Department [...] Read more.
Respiratory infections represent one of the leading causes of pediatric consultations and hospitalizations in Chile, where rapid etiological identification is essential for clinical decision-making. We evaluated the impact of implementing the BIOFIRE® SPOTFIRE® Respiratory (R) Panel in the pediatric Emergency Department of a public referral hospital in Santiago, using a pre–post cross-sectional design comparing two winter periods (July 2023 vs. July 2024). Clinical records, laboratory data, and operational indicators were analyzed to assess changes in diagnostic yield, turnaround time, hospitalizations, discharges, supplementary test requests, and antimicrobial use. A total of 470 patients were included (224 in 2023; 246 in 2024). The etiological detection rate increased from 58.0% to 87.8% after the implementation of Spotfire® (p < 0.0001), with marked increases in the identification of adenovirus, RSV, rhinovirus/enterovirus, and seasonal coronaviruses. Rapid molecular testing was associated with a significant rise in emergency department discharges (23.7% vs. 57.3%; p < 0.0001) and a reduction in hospitalizations (76.3% vs. 42.7%; p < 0.0001) and readmissions (9.2% vs. 0.5%; p < 0.0001). Requests for complete blood counts, chest X-rays, and antimicrobial prescriptions at discharge also decreased significantly. These effects persisted in key subgroups, including infants and children with comorbidities. In this high-demand winter setting, the BIOFIRE® SPOTFIRE® R Panel improved diagnostic performance and supported more efficient and targeted clinical management. Full article
(This article belongs to the Special Issue RSV Epidemiological Surveillance: 2nd Edition)
20 pages, 7004 KB  
Article
Genetic Diversity of SARS-CoV-2 in Kazakhstan from 2020 to 2022
by Altynay Gabiden, Andrey Komissarov, Aknur Mutaliyeva, Aidar Usserbayev, Kobey Karamendin, Alexander Perederiy, Artem Fadeev, Ainagul Kuatbaeva, Dariya Jussupova, Askar Abdaliyev, Manar Smagul, Yelizaveta Khan, Marat Kumar, Temirlan Sabyrzhan, Aigerim Abdimadiyeva and Aidyn Kydyrmanov
Viruses 2026, 18(1), 138; https://doi.org/10.3390/v18010138 - 21 Jan 2026
Viewed by 415
Abstract
Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has had major social and economic consequences worldwide. Whole genome sequencing (WGS) is essential for genomic monitoring, enabling tracking of viral evolution, detection of emerging variants, and identification of introductions and transmission chains to inform timely [...] Read more.
Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has had major social and economic consequences worldwide. Whole genome sequencing (WGS) is essential for genomic monitoring, enabling tracking of viral evolution, detection of emerging variants, and identification of introductions and transmission chains to inform timely public health responses. Here, we compile and harmonize SARS-CoV-2 genomic data generated by multiple laboratories across Kazakhstan together with publicly available sequences to provide a national overview of genomic dynamics across successive epidemic waves from 2020 to 2022. We analyzed 4462 genomes deposited in GISAID (including 340 generated in this study), of which 3299 passed Nextclade quality filters, and summarized lineage turnover across major phases (pre-VOC, Alpha, Delta, Omicron BA.1/BA.2, Omicron BA.4/BA.5, and a later recombinant-dominant period). Sequencing intensity varied markedly over time (0.60‰ of confirmed cases during Delta vs. 11.57‰ during the Omicron BA.5 wave), suggesting that lineage diversity and persistence may be underestimated. Pre-VOC circulation included ≥12 Pango lineages with evidence of multiple introductions and sustained local transmission, including a Kazakhstan-restricted B.4.1 lineage that emerged in Nur-Sultan/Astana and disappeared after April 2020. The Tengizchevroil oilfield outbreak comprised B.1.1 viruses with phylogenetic support for ≥three independent introductions. Alpha and Omicron waves were characterized by repeated introductions and heterogeneous origins, whereas Delta was dominated by AY.122 with an additional distinct AY.122 cluster; a notable BF.7 local transmission event was observed during BA.5. We also highlight locally enriched non-lineage-defining mutations. Overall, recurrent importations and variable local amplification shaped SARS-CoV-2 dynamics in Kazakhstan, while interpretation is constrained by strongly time-skewed sequencing. Full article
(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 4th Edition)
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18 pages, 5071 KB  
Article
The Introduction of a HuR-Binding Site in the 3′ UTR and the CD47 Cytoplasmic Tail Enhances SARS-CoV-2 S-Protein Expression in Cells
by Ivan M. Pereverzev, Irina A. Bakhno, Kristina I. Yakovleva, Ilya S. Dovydenko and Evgeniya E. Burkova
Viruses 2026, 18(1), 137; https://doi.org/10.3390/v18010137 - 21 Jan 2026
Viewed by 214
Abstract
In this study, we constructed plasmids to increase the overall expression level of the SARS-CoV-2 S-protein and its presentation on the cell surface. To this end, we designed a series of plasmid constructs encoding the SARS-CoV-2 S-protein with modifications to its cytoplasmic domain [...] Read more.
In this study, we constructed plasmids to increase the overall expression level of the SARS-CoV-2 S-protein and its presentation on the cell surface. To this end, we designed a series of plasmid constructs encoding the SARS-CoV-2 S-protein with modifications to its cytoplasmic domain and containing various 5′ and 3′ untranslated regions. Our results confirmed the critical role of the S-protein cytoplasmic domain in limiting its localization to the cell surface. We confirmed that deletion of the 19 C-terminal amino acids, which contain an endoplasmic reticulum retrieval signal, significantly increased S-protein presentation on the cell surface. Furthermore, introducing the HuR-binding site from the CD47 3′ untranslated region and replacing the 19 C-terminal amino acids of the S-protein with the CD47 cytoplasmic tail significantly enhanced total S-protein expression compared to the wild-type S-protein and constructs with the 19-amino-acid deletion. Unfortunately, for the plasmid constructs bearing CD47 elements, their higher surface expression compared to the wild-type S-protein correlated with a high total protein expression level. Full article
(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals (2nd Edition))
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23 pages, 4838 KB  
Article
Nationwide Genomic Surveillance of Human Respiratory Adenoviruses in 2023–2024: Evidence of Extensive Diversity and Recombination in Russia
by Nikita D. Yolshin, Anna A. Ivanova, Alexander A. Perederiy, Irina V. Amosova, Tatyana A. Timoshicheva, Kirill A. Stolyarov, Daria M. Danilenko, Dmitry A. Lioznov and Andrey B. Komissarov
Viruses 2026, 18(1), 136; https://doi.org/10.3390/v18010136 - 21 Jan 2026
Viewed by 273
Abstract
Human adenoviruses (HAdVs) are globally distributed pathogens capable of causing a wide range of clinical manifestations, particularly acute respiratory infections. However, their genomic diversity remains insufficiently characterized, with substantial geographic gaps in available sequence data, including for Russia, where only a few complete [...] Read more.
Human adenoviruses (HAdVs) are globally distributed pathogens capable of causing a wide range of clinical manifestations, particularly acute respiratory infections. However, their genomic diversity remains insufficiently characterized, with substantial geographic gaps in available sequence data, including for Russia, where only a few complete genomes have been deposited prior to this work. In this study, we analyzed more than 1200 PCR-positive respiratory specimens collected from hospitalized patients within routine surveillance projects and the Global Influenza Hospital Surveillance Network (GIHSN) across plenty of Russian regions during 2023–2024. Virus isolation followed by next-generation sequencing yielded 128 complete HAdV genomes representing species B, C, and D. The dataset included 27 B3, 9 B7, 44 B55, 12 C1, 16 C2, 4 C5, 7 C89, 5 C108, and one D109 genome, as well as three unassigned recombinant viruses with p89h5f5, p5h6f6 and p5h57f6 genomic structures (p, penton base; h, hexon; f, fiber). Phylogenetic analyses of whole genomes and capsid genes revealed extensive variability in immunogenic regions, particularly in species C, and identified clusters within B3 viruses. Notably, HAdV-D109 was identified in Russia, marking only the second reported detection of this genotype worldwide. Together, these findings substantially expand the currently available genomic landscape of HAdVs, highlighting the circulation of diverse and recombinant strains in Russia. Full article
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17 pages, 641 KB  
Article
Clinical, Demographic, and Virological Predictors of Hospital Admission in Patients with Acute Viral Respiratory Infections: A Retrospective Observational Study
by Karolina Akinosoglou, Nikolaos Theofanis, Konstantinos Asimos, Michail Michailidis, Despoina Papageorgiou, Eleni Polyzou and Charalambos Gogos
Viruses 2026, 18(1), 135; https://doi.org/10.3390/v18010135 - 21 Jan 2026
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Abstract
Background: Viral respiratory tract infections (RTIs) frequently lead to emergency department (ED) presentations and hospital admissions, particularly among older adults and individuals with underlying health conditions. Identifying patients at increased risk for hospitalization is essential for optimizing triage and resource allocation. This study [...] Read more.
Background: Viral respiratory tract infections (RTIs) frequently lead to emergency department (ED) presentations and hospital admissions, particularly among older adults and individuals with underlying health conditions. Identifying patients at increased risk for hospitalization is essential for optimizing triage and resource allocation. This study aimed to determine independent demographic, clinical, and virological predictors of hospital admission among adults presenting with confirmed viral RTIs. Methods: A retrospective cohort study was conducted at a tertiary hospital between September 2022 and May 2024. Adult patients with molecularly confirmed viral RTIs were included. Demographic, clinical, and microbiological data were extracted from electronic medical records. Predictors of admission were assessed using univariate and multivariate logistic regression. Results: Among 311 patients, 147 (47.3%) required hospitalization. Hospitalized patients were significantly older and more likely to present with fever, cough, tachypnea, dyspnea, chest pain, comorbidities, and lower or mixed respiratory tract infections (all p < 0.001). In multivariate analysis, older age, fever, cough, and lower or mixed RTIs were strong independent predictors of admission. Several viral pathogens, including human rhinovirus, non–SARS-CoV-2 coronaviruses, influenza A, and parainfluenza virus, were associated with reduced odds of hospitalization. Conclusions: Age, comorbidity burden, and lower respiratory tract involvement are key determinants of hospitalization in viral RTIs. Integrating clinical and virological data may improve risk stratification and guide ED triage during seasonal and emerging respiratory virus activity. Full article
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15 pages, 2017 KB  
Article
Transmembrane Domain Length of Influenza a Virus M2 Does Not Determine Its Non-Lipid Raft Localization
by Rashid Manzoor, Kosuke Okuya, Reiko Yoshida, Hiroko Miyamoto and Ayato Takada
Viruses 2026, 18(1), 134; https://doi.org/10.3390/v18010134 - 21 Jan 2026
Viewed by 300
Abstract
Influenza A virus expresses three envelope proteins, hemagglutinin (HA), neuraminidase (NA), and matrix protein 2 (M2). Of these, HA and NA associate with lipid rafts, whereas M2 remains in the peri-raft region. One reason for the lipid raft association of HA and NA [...] Read more.
Influenza A virus expresses three envelope proteins, hemagglutinin (HA), neuraminidase (NA), and matrix protein 2 (M2). Of these, HA and NA associate with lipid rafts, whereas M2 remains in the peri-raft region. One reason for the lipid raft association of HA and NA is that they possess longer transmembrane domains (TMDs) (27 and 29 amino acids, respectively) than that of M2 (19 amino acids). Moreover, M2 localizes in the peri-raft region, despite the presence of some lipid raft-targeting features. Therefore, we introduced amino acid insertions into the N-terminal region of M2 to increase the TMD length to 22, 25, and 27 residues, and evaluated these M2-TMD mutants for their association with lipid rafts and impact on virus replication. Confocal microscopy, immunoprecipitation, and cell cytotoxicity assays showed that the cell surface expression and cytotoxic potential of M2-TMD mutants were comparable to those of wildtype M2. Based on the Triton X-100 solubility assay and colocalization analysis between lipid rafts and M2-TMD mutants, we found that the mutant proteins largely remained localized in non-raft domains. Importantly, an increase in M2-TMD length negatively influenced viral replication. These findings suggest that M2-TMD length is optimized for its proper function and does not determine its association with lipid raft domains. Full article
(This article belongs to the Special Issue Interaction Between Influenza Virus and Host Cell)
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18 pages, 548 KB  
Article
Respiratory Syncytial Virus Positivity Rate and Clinical Characteristics Amongst Children Under 5 Years of Age at the Emergency and Outpatient Settings in Jordan: A Cross-Sectional Study
by Munir Abu-Helalah, Samah F. Al-Shatnawi, Mohammad Abu Lubad, Enas Al-Zayadneh, Mohammad Al-Hanaktah, Mea’ad Harahsheh, Montaha Al-Iede, Ruba Yousef, Mai Ababneh, Toqa AlZubi, Suad Abu Khousa, Mohammad Al Tamimi and Simon B. Drysdale
Viruses 2026, 18(1), 133; https://doi.org/10.3390/v18010133 - 20 Jan 2026
Viewed by 328
Abstract
Background: Acute viral respiratory infections are a major cause of morbidity among young children, with respiratory syncytial virus (RSV) being the leading pathogen. In Jordan and globally, most RSV research has focused on hospitalized patients, while data from emergency departments (EDs) and outpatient [...] Read more.
Background: Acute viral respiratory infections are a major cause of morbidity among young children, with respiratory syncytial virus (RSV) being the leading pathogen. In Jordan and globally, most RSV research has focused on hospitalized patients, while data from emergency departments (EDs) and outpatient settings remain limited. Methods: This cross-sectional study was conducted at two major Jordanian hospitals between November 2022 and March 2023. Children under five years of age presenting to EDs or outpatient clinics with symptoms of acute respiratory infection were enrolled. Nasopharyngeal specimens were tested for RSV, and subtypes (RSV-A and RSV-B) were identified using multiplex RT-PCR. Results: Of 229 enrolled children, 92 (40.2%) tested positive for RSV, with RSV-B accounting for 81.5% of positive cases. RSV positivity was higher in ED presentations than in outpatient clinics (46% vs. 35%). Wheezing (72.8% vs. 39.4%, p < 0.001) and dyspnea (33.7% vs. 14.6%, p = 0.001) were significantly more frequent among RSV-positive patients. Independent predictors of RSV positivity included non-referred outpatient visits (OR = 15.26), non-referred ED visits (OR = 42.93), younger age, and prior systemic steroid use. Conclusions: RSV poses a substantial burden in outpatient and ED settings. Identified demographic and clinical predictors may help target high-risk groups for future preventive interventions. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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16 pages, 19905 KB  
Article
Immune Imprinting Identified in Phage-Display Antibody Libraries Derived from Early Wild-Type and Late Omicron COVID-19 Convalescents
by Boyang Li, Mengxuan Wang, Fang Huang, Wei Wu, Jiaxin Fan, Lu Yang, Yongbing Pan, Mifang Liang and Kai Duan
Viruses 2026, 18(1), 132; https://doi.org/10.3390/v18010132 - 20 Jan 2026
Viewed by 295
Abstract
The rapid evolution of SARS-CoV-2, particularly the emergence of Omicron subvariants, has significantly reduced the efficacy of existing vaccines and monoclonal antibodies. This study investigates the phenomenon of immune imprinting by comparing two phage display antibody libraries derived from early 2020 wild-type SARS-CoV-2 [...] Read more.
The rapid evolution of SARS-CoV-2, particularly the emergence of Omicron subvariants, has significantly reduced the efficacy of existing vaccines and monoclonal antibodies. This study investigates the phenomenon of immune imprinting by comparing two phage display antibody libraries derived from early 2020 wild-type SARS-CoV-2 convalescents (WT-AbLib) and early 2023 Omicron convalescents (Omi-AbLib). The capacity and diversity of both antibody libraries were systematically evaluated. The libraries were screened using BF.7 and XBB.1.5 antigens. WT-AbLib showed markedly reduced diversity after Omicron antigen selection, with dominant clones shifting from IGHV3-66-class broadly neutralizing antibodies (bnAbs) targeting the receptor-binding motif to IGHV1-46-class broadly non-neutralizing antibodies targeting conserved lateral receptor-binding domain (RBD) sites. Omi-AbLib maintained higher diversity, but dominant antibodies were also non-neutralizing and targeted the same conserved lateral region. These findings suggest that immune imprinting drives the dominance of broadly non-neutralizing antibodies following Omicron breakthrough or reinfection. This phenomenon provides a mechanistic explanation for persistent viral evasion and recurrent infection, and highlights major challenges for the development of next-generation broadly neutralizing therapeutics. Full article
(This article belongs to the Special Issue SARS-CoV-2 Neutralizing Antibodies, 3rd Edition)
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14 pages, 5669 KB  
Article
Structural Insights into the Interaction Between a Core-Fucosylated Foodborne Hexasaccharide (H2N2F2) and Human Norovirus P Proteins
by Zilei Zhang, Yuchen Wang, Jiaqi Xu, Fei Liu, Shumin Li, Justin Troy Cox, Liang Xue and Danlei Liu
Viruses 2026, 18(1), 131; https://doi.org/10.3390/v18010131 - 20 Jan 2026
Viewed by 187
Abstract
Background: Human noroviruses are the leading cause of foodborne gastroenteritis worldwide. Accumulating evidence suggests that food matrices containing fucosylated or histo-blood group antigen (HBGA)-like glycans may facilitate viral attachment and persistence, yet the molecular mechanisms underlying these interactions remain unclear. Methods: In this [...] Read more.
Background: Human noroviruses are the leading cause of foodborne gastroenteritis worldwide. Accumulating evidence suggests that food matrices containing fucosylated or histo-blood group antigen (HBGA)-like glycans may facilitate viral attachment and persistence, yet the molecular mechanisms underlying these interactions remain unclear. Methods: In this study, we performed a comparative computational analysis of norovirus–glycan interactions by integrating AlphaFold3-based structure prediction, molecular docking, and molecular dynamics simulations. A total of 182 P-domain models representing all genotypes across five human norovirus genogroups (GI, GII, GIV, GVIII, and GIX) were predicted and docked with a lettuce-derived core-fucosylated hexasaccharide (H2N2F2) previously identified by our group. The three complexes exhibiting the most favorable docking energies were further examined using 40 ns molecular dynamics simulations, followed by MM/GBSA binding free energy calculations and per-residue decomposition analyses. Results: Docking results indicated that the majority of modeled P proteins were able to adopt energetically favorable interaction poses with H2N2F2, with predicted binding energies ranging from −3.7 to −7.2 kcal·mol−1. The most favorable docking energies were observed for GII.6_S9c_KC576910 (−7.2 kcal·mol−1), GII.3_MX_U22498 (−7.1 kcal·mol−1), and GII.4_CARGDS11182_OR700741 (−6.8 kcal·mol−1). Molecular dynamics simulations suggested stable ligand engagement within canonical HBGA-binding pockets, with recurrent residues such as Asp374, Gln393, and Arg345 contributing to electrostatic and hydrophobic interactions, consistent with previously reported HBGA-binding motifs. MM/GBSA analyses revealed comparatively favorable binding tendencies among these complexes, particularly for globally prevalent genotypes including GII.3, GII.4, and GII.6. Conclusions: This work provides a large-scale structural and energetic assessment of the potential interactions between a naturally occurring lettuce-derived fucosylated hexasaccharide and human norovirus P domains. The results support the notion that core-fucosylated food-associated glycans can serve as interaction partners for diverse norovirus genotypes and offer comparative molecular insights into glycan recognition patterns relevant to foodborne transmission. The integrative AlphaFold3–docking–dynamics framework presented here may facilitate future investigations of virus–glycan interactions within food matrices. Full article
(This article belongs to the Special Issue Food-Associated and Foodborne Viruses: A Food Safety Concern or Tool?)
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16 pages, 2739 KB  
Article
Changing Trends of Respiratory Viruses in Hospitalized Children During and After the COVID-19 Emergency Phase in Yongin, South Korea (2020–22 vs. 2023–24)
by Joon-sik Choi, Eun Gyeong Seol, Ji Hyun Lee, Heejung Kim, Kyung Min Choi and Min Jung Kim
Viruses 2026, 18(1), 130; https://doi.org/10.3390/v18010130 - 20 Jan 2026
Viewed by 293
Abstract
The COVID-19 pandemic and subsequent non-pharmaceutical interventions (NPIs) significantly disrupted the epidemiology of pediatric respiratory viruses. This study compared infection patterns among 3658 hospitalized children in South Korea during the pandemic (2020–2022) and the post-emergency phase (2023–2024), following the relaxation of mandatory NPIs. [...] Read more.
The COVID-19 pandemic and subsequent non-pharmaceutical interventions (NPIs) significantly disrupted the epidemiology of pediatric respiratory viruses. This study compared infection patterns among 3658 hospitalized children in South Korea during the pandemic (2020–2022) and the post-emergency phase (2023–2024), following the relaxation of mandatory NPIs. Of 4419 eligible tests, the most frequently detected viruses overall were rhinovirus/enterovirus (HRV/HEV) (27.9%), influenza (14.5%), and respiratory syncytial virus (RSV, 11.9%). The post-emergency phase was marked by a dramatic surge in influenza virus (IFV), which surged dramatically (5.5% → 28.2%), and a more than two-fold increase in adenovirus (ADV) (5.7% → 12.5%) (p < 0.001). (p < 0.001). Conversely, parainfluenza virus (PIV) detection rates declined significantly (15.4% → 11.3%, p < 0.001). Demographically, post-emergency phase patients were significantly older (mean 4.9 vs. 3.5 years) and experienced a shorter hospital stays (3.2 vs. 4.3 days) (p < 0.001). Crucially, age-specific susceptibility shifts were evident. IFV rebounded across all pediatric ages but spiked severely in school-aged children and adolescents, while HRV/HEV demonstrated a clear proportional shift towards older age groups. These results demonstrate a substantial reconfiguration of the pediatric respiratory landscape, necessitating age-stratified surveillance and flexible public health strategies to mitigate the future infectious disease burden. Full article
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16 pages, 3342 KB  
Article
Comprehensive Transcriptomic Profiling Reveals Rotavirus-Induced Alterations in Both Coding and Long Non-Coding RNA Expression in MA104 Cells
by Xiaopeng Song, Yanwei Wu, Xiaocai Yin, Xiaoqing Hu, Jinyuan Wu, Xiangjing Kuang, Rong Chen, Xiaochen Lin, Jun Ye, Guangming Zhang, Maosheng Sun, Yan Zhou and Hongjun Li
Viruses 2026, 18(1), 129; https://doi.org/10.3390/v18010129 - 20 Jan 2026
Viewed by 216
Abstract
Rotavirus (RV) is the primary cause of severe gastroenteritis in young children, yet the long noncoding RNA (lncRNA) regulatory landscape governing the host response remains largely unmapped. To address this gap, the present study performed an integrated transcriptomic analysis of mRNA and lncRNA [...] Read more.
Rotavirus (RV) is the primary cause of severe gastroenteritis in young children, yet the long noncoding RNA (lncRNA) regulatory landscape governing the host response remains largely unmapped. To address this gap, the present study performed an integrated transcriptomic analysis of mRNA and lncRNA expression profiles in RV-infected MA104 cells at 24 h post-infection. Deep sequencing identified 11,919 high-confidence lncRNAs, revealing a massive transcriptional shift: 3651 mRNAs and 4655 lncRNAs were differentially expressed, with both populations predominantly upregulated. Functional enrichment analysis confirmed the strong activation of key innate immunity pathways, including the RIG-I-like receptor, Toll-like receptor, and TNF signaling pathways. Conversely, fundamental metabolic pathways were found to be suppressed. Crucially, the analysis of lncRNA targets highlighted their involvement in coordinating the host antiviral defense, particularly through transregulation. Experimental validation confirmed the significant upregulation of key immune-related mRNAs (OASL and C3) as well as two novel lncRNAs (lncRNA-6479 and lncRNA-4290) by qRT-PCR. The significant upregulation of OASL and C3 was validated at the protein level, confirming the biological relevance of the transcriptomic data. This study provides a foundational, genome-wide resource, identifying novel lncRNA targets for future mechanistic investigation into host–RV interactions. Full article
(This article belongs to the Special Issue Functional RNAs in Virology)
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18 pages, 762 KB  
Review
Making Sense from Structure: What the Immune System Sees in Viral RNA
by Benjamin J. Cryer and Margaret J. Lange
Viruses 2026, 18(1), 128; https://doi.org/10.3390/v18010128 - 20 Jan 2026
Viewed by 343
Abstract
Viral RNA structure plays a critical regulatory role in viral replication, serving as a dual-purpose mechanism for encoding genetic information and controlling biological processes. However, these structural elements also serve as pathogen-associated molecular patterns (PAMPs), which are recognized by pattern recognition receptors (PRRs) [...] Read more.
Viral RNA structure plays a critical regulatory role in viral replication, serving as a dual-purpose mechanism for encoding genetic information and controlling biological processes. However, these structural elements also serve as pathogen-associated molecular patterns (PAMPs), which are recognized by pattern recognition receptors (PRRs) of the host innate immune system. This review discusses the complex and poorly understood relationship between viral RNA structure and recognition of RNA by PRRs, specifically focusing on Toll-like receptor 3 (TLR3) and Retinoic acid-inducible gene I (RIG-I). While current interaction models rely upon data generated from use of synthetic ligands such as poly(I:C) or perfectly base-paired double-stranded RNA stems, this review highlights significant gaps in our understanding of how PRRs recognize naturally occurring viral RNAs that fold into highly complex three-dimensional structures. Furthermore, we explore how viral evolution and nucleotide variations, such as those observed in influenza viruses, can drastically alter local and distal RNA structure, potentially impacting immune detection. We conclude that moving beyond synthetic models to understand natural RNA structural dynamics is essential for elucidating the mechanisms of viral immune evasion and pathogenesis. Full article
(This article belongs to the Section General Virology)
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4 pages, 159 KB  
Editorial
Aquatic Animal Viruses and Antiviral Immunity: A Closing Editorial
by Mark P. Polinski
Viruses 2026, 18(1), 127; https://doi.org/10.3390/v18010127 - 20 Jan 2026
Viewed by 199
Abstract
Aquatic ecosystems host the planet’s greatest animal diversity, and with it, a remarkably varied virosphere [...] Full article
(This article belongs to the Special Issue Aquatic Animal Viruses and Antiviral Immunity)
32 pages, 10393 KB  
Systematic Review
Respiratory Syncytial Virus Prevalence and Genotypic Distribution in the Countries of the Former Soviet Union: A Systematic Review and Meta-Analysis
by Denis E. Maslov, Ivan D. Osipov, Daria S. Zabelina, Anastasia A. Pak and Sergey V. Netesov
Viruses 2026, 18(1), 126; https://doi.org/10.3390/v18010126 - 19 Jan 2026
Viewed by 430
Abstract
Respiratory syncytial virus (RSV) is among leading global causes of lower respiratory tract infections, yet data from Russia and other states of the Former Soviet Union (FSU) remain fragmented and structurally inconsistent. This systematic review aims to map and synthesize existing evidence on [...] Read more.
Respiratory syncytial virus (RSV) is among leading global causes of lower respiratory tract infections, yet data from Russia and other states of the Former Soviet Union (FSU) remain fragmented and structurally inconsistent. This systematic review aims to map and synthesize existing evidence on RSV epidemiology and genotypic distribution across the FSU. Published studies from eLIBRARY and PubMed databases queried for RSV prevalence data, together with public health surveillance datasets, were used to summarize RSV prevalence research across eight FSU countries. Random-effects meta-analysis across age strata showed high prevalence in children before 6 (21%) and a progressive decline with age, which is in agreement with global data. Prevalence estimates showed a high degree of variability partially explained by study scope and clinical presentation. We observed COVID-19-related seasonal disruptions of RSV seasonality, followed by gradual post-pandemic stabilization. Genotypic data reflects global trends with two cosmopolitan clades, A.D and B.D, and their descendants, dominating in the region. The review is limited by uneven geographical and temporal coverage, and scarce data on adults. The review provides the first integrated summary of RSV epidemiology across the FSU and underscores the need for expanded regional surveillance and genomic reporting. Full article
(This article belongs to the Special Issue RSV Epidemiological Surveillance: 2nd Edition)
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19 pages, 1243 KB  
Review
Host Cell Virus Interactions: Molecular Mechanisms, Immune Modulation, Viral Pathogenesis, and Emerging Therapeutic Targets
by Awadh Alanazi, Mohamed N. Ibrahim, Eman Fawzy El Azab and Mohamed A. Elithy
Viruses 2026, 18(1), 125; https://doi.org/10.3390/v18010125 - 18 Jan 2026
Viewed by 695
Abstract
Host–virus relationships regulate every phase of viral infection and critically influence course of illness and the effectiveness of treatment. Viruses utilize host receptors, intracellular trafficking routes, metabolic programs, and immunological signaling networks to introduce infection, while host cells use innate and adaptive immune [...] Read more.
Host–virus relationships regulate every phase of viral infection and critically influence course of illness and the effectiveness of treatment. Viruses utilize host receptors, intracellular trafficking routes, metabolic programs, and immunological signaling networks to introduce infection, while host cells use innate and adaptive immune responses that both limit viral replication and, in certain situations, cause tissue damage. Given the fast viral evolution and drug resistance linked to virus-directed therapy, there is growing proof that these host-dependent mechanisms are appealing and underutilized targets for antiviral treatment. Recent developments in single-cell technology, proteomics, and functional genomics have made it possible to systematically identify host dependency and restriction factors shared by different viral families, exposing common molecular vulnerabilities that might be targeted therapeutically. This review integrates current knowledge of virus–host interplay via a translational lens, highlighting processes that directly guide the formation of host-directed antivirals and immune-regulating treatments. We emphasize host processes involved in viral entry, replication, and immune signaling that have shown therapeutic significance, while illustrating the difficulties of balancing antiviral effectiveness with immunopathology. By framing host–virus interactions through a therapeutic lens, this review attempts to offer a targeted and translationally relevant viewpoint for next-generation antiviral research. Full article
(This article belongs to the Special Issue Host Cell-Virus Interaction, 4th Edition)
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13 pages, 916 KB  
Article
Development of an Indirect ELISA for REV gp90 Antibody Detection Using the gp90 Protein Expressed in Suspended Cells
by Erjing Ke, Mengmeng Huang, Guodong Wang, Jingzhe Han, Yulong Zhang, Runhang Liu, Hangbo Yu, Ziwen Wu, Dan Ling, Xianyun Liu, Tengfei Xu, Suyan Wang, Yuntong Chen, Yongzhen Liu, Yanping Zhang, Hongyu Cui, Yulu Duan, Liuan Li, Xiaoxue Yu, Yulong Gao and Xiaole Qiadd Show full author list remove Hide full author list
Viruses 2026, 18(1), 124; https://doi.org/10.3390/v18010124 - 17 Jan 2026
Viewed by 320
Abstract
Reticuloendotheliosis virus (REV) is an immunosuppressive virus in poultry that can cause acute reticular neoplasms, chronic lymphoid tumors, stunting syndrome, and secondary infections. In many countries, the lack of effective vaccines has resulted in a high prevalence of REV infections and substantial economic [...] Read more.
Reticuloendotheliosis virus (REV) is an immunosuppressive virus in poultry that can cause acute reticular neoplasms, chronic lymphoid tumors, stunting syndrome, and secondary infections. In many countries, the lack of effective vaccines has resulted in a high prevalence of REV infections and substantial economic losses. Enzyme-linked immunosorbent assay (ELISA)-based antibody detection is an important tool for monitoring the REV prevalence in poultry farms. ELISA coating antigens generally consist of either whole virus or viral protein; however, most commercially available REV antibody ELISA detection kits use whole virus as the coating antigen, which limits their applicability in certain diagnostic and research settings. In this study, the gp90 protein from a dominant REV strain was expressed and purified using 293F suspension cell eukaryotic expression system. Using recombinant gp90 protein as the coating antigen, an indirect ELISA for detecting gp90 antibodies (gp90-ELISA) was developed. After optimization, the optimal conditions were as follows: coating antigen concentration of 4 µg/mL with overnight incubation at 4 °C; blocking with 5% skim milk at 37 °C for 1.5 h; serum dilution of 1:200 with incubation at 37 °C for 45 min; secondary antibody dilution of 1:1000 with incubation at 37 °C for 30 min; and color development using TMB substrate at room temperature in the dark for 10 min. The cut-off value was defined as an OD450 ≥ 0.22 for positive samples and <0.22 for negative samples. The developed gp90-ELISA specifically detected REV-positive sera at a maximum serum dilution ratio of 1:3200. Intra- and inter-assay variation coefficients were ≤10%, indicating that the gp90-ELISA had good specificity, sensitivity, and reproducibility. Laboratory serum testing showed that the gp90-ELISA successfully detected sera from chickens immunized with the gp90 protein or infected with REV. Furthermore, analysis of clinical serum samples demonstrated 100% concordance between the gp90-ELISA results and a commercial whole-virus-coated ELISA kit. These results indicate that the gp90-ELISA is a reliable supplementary method to whole-virus-coated ELISA and has potential utility in disease surveillance and evaluation of immune responses. Full article
(This article belongs to the Section Animal Viruses)
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12 pages, 1500 KB  
Article
Detection and Molecular Characterisation of Protoparvovirus carnivoran1 in Golden Jackals (Canis aureus) in Croatia
by Ivona Coric, Gorana Miletic, Dean Konjevic, Ivica Boskovic, Miljenko Bujanic, Alenka Skrinjaric, Snjezana Kovac, Ljubo Barbic, Andreja Jungic and Vladimir Stevanovic
Viruses 2026, 18(1), 123; https://doi.org/10.3390/v18010123 - 17 Jan 2026
Viewed by 360
Abstract
Protoparvoviruses are highly contagious pathogens that cause severe, often fatal diseases in both domestic and wild carnivores. Golden jackal (Canis aureus) populations have experienced expansion in recent years, increasingly occupying urban and peri-urban areas. Despite this, they remain largely overlooked in [...] Read more.
Protoparvoviruses are highly contagious pathogens that cause severe, often fatal diseases in both domestic and wild carnivores. Golden jackal (Canis aureus) populations have experienced expansion in recent years, increasingly occupying urban and peri-urban areas. Despite this, they remain largely overlooked in scientific research. This study aimed to detect and characterise Protoparvovirus carnivoran1 circulating in a golden jackal population in Croatia and to assess their role in the epidemiology of parvovirus infections in companion animals. Small intestines from 55 jackals hunted in 2024 and 2025 were tested for Protoparvovirus carnivoran1 using real-time PCR. Positive samples were found across all sampling sites, with an overall positivity rate of 40%. Based on characteristic amino acid residues within the VP2 protein, the viruses detected in jackals were classified as feline panleukopenia virus (FPV). Phylogenetic analysis of the VP2 protein demonstrated considerable genetic diversity among strains circulating in Croatia. Additionally, a distinct group was identified, shared exclusively by Croatian domestic cats and golden jackals. Amino acid analysis revealed the novel A91T mutation, found only in jackals, and the E411Q mutation, unique to Croatian FPV strains. Structural modelling of the VP2 protein indicates that the observed mutations are located on the protein surface, within the antibody-binding site. These findings highlight the potential role of wild carnivores in parvovirus epidemiology and underscore the importance of including them in future surveillance and research efforts. Full article
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18 pages, 1487 KB  
Article
Cognitive Flexibility and Inhibition Deficits in HIV and Cocaine Dependence: Evidence from Stroop and Trail Making Tests
by Sarah E. Nigro, Minjie Wu, Betty Jo Salmeron, Sharmin Islam-Souleimanova, Eve Lauer, Anthony C. Juliano, Alinda R. Lord, Atash Sabet, Lisa H. Lu, T. Celeste Napier, Audrey L. French, Howard J. Aizenstein, Yihong Yang and Shaolin Yang
Viruses 2026, 18(1), 122; https://doi.org/10.3390/v18010122 - 16 Jan 2026
Viewed by 413
Abstract
Objective: To better define potential executive function difficulties in individuals living with HIV but not clinically identified as having HAND, with and without mild to moderate cocaine dependence (CD), our cross-sectional study examined executive function performance on the Stroop Color-Word Test (Stroop) and [...] Read more.
Objective: To better define potential executive function difficulties in individuals living with HIV but not clinically identified as having HAND, with and without mild to moderate cocaine dependence (CD), our cross-sectional study examined executive function performance on the Stroop Color-Word Test (Stroop) and the Trail Making Test (TMT) in four groups stratified by HIV and CD status. Method: We recruited 101 participants (26 HIV+/CD+; 18 HIV+/CD−; 30 HIV−/CD+; 27 HIV−/CD−). We utilized a 2 (HIV: yes/no) × 2 (Cocaine: yes/no) MANCOVA while controlling for age and premorbid intelligence on the Stroop trials (i.e., color-naming, word-reading, interference), and TMT-A and TMT-B z-scores, number of errors, and the B/A ratio. Results: HIV was associated with significantly slower performance on the Stroop Interference (p = 0.012, η2 = 0.064). CD showed a trend towards slower performance on interference trials (p = 0.061, η2 = 0.037) and was associated with significantly more errors on the Stroop Word-Reading (p = 0.028, η2 = 0.050) and Interference trials (p = 0.046, η2 = 0.041), suggestive of difficulties with inhibitory control and written language processing. There were no significant HIV × Cocaine interactions. Conclusions: Our results suggest HIV without clinically identified cognitive impairment and CD are associated with distinct and potentially overlapping executive functioning deficits, particularly for measures of inhibitory control. Notably, CD showed trend-level slowing on Stroop Interference performance, suggesting partial overlap with HIV effects. Clarifying the specific cognitive processes impacted by HIV and CD can help guide tailored interventions to improve functional outcomes in these populations. Full article
(This article belongs to the Special Issue HIV Neurological Disorders: 2nd Edition)
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16 pages, 1942 KB  
Article
Genetic Diversity of the Non-Polio Enteroviruses Detected in Samples of Patients with Aseptic Meningitis in the Ural Federal District and Western Siberia
by Tarek M. Itani, Vladislav I. Chalapa, Anastasia K. Patrusheva, Evgeniy S. Kuznetsov and Aleksandr V. Semenov
Viruses 2026, 18(1), 121; https://doi.org/10.3390/v18010121 - 16 Jan 2026
Viewed by 313
Abstract
Human non-polio enteroviruses (NPEVs) cause a plethora of infections in humans, ranging from mild to severe neurological diseases including aseptic meningitis. NPEVs are the leading cause of aseptic meningitis in both children and adults worldwide. In Russia, reports of NPEV infections have surged, [...] Read more.
Human non-polio enteroviruses (NPEVs) cause a plethora of infections in humans, ranging from mild to severe neurological diseases including aseptic meningitis. NPEVs are the leading cause of aseptic meningitis in both children and adults worldwide. In Russia, reports of NPEV infections have surged, especially in the post-COVID era starting in 2022, with elevated infection rates into 2023. A comprehensive examination of the whole genome is crucial for understanding the evolution of NPEV genes and for predicting potential outbreaks. This study focused on identifying the circulating NPEV strains in the Ural Federal District and Western Siberia, using Sanger sequencing and next-generation sequencing (NGS) methodologies. Biological samples were collected from (n = 225) patients diagnosed with aseptic meningitis. Bioinformatics analysis targeted the nucleotide sequences of the major capsid protein (partial VP1) gene fragment, and the assembly of whole NPEV genomes. A total of 159 NPEVs were characterized, representing 70.7% of the collected samples. The main capsid variants forming the predominant genotypic profile included E30 (n = 39, 24.3%), E6 (n = 31, 19.3%), and CVA9 (n = 25, 15.6%). Using NGS, we successfully assembled 13 whole genomes for E6, E30, EV-B80, CVA9, CVB5, E11, and EV-A71 and 3 partial genomes for E6 and EV-B87. This molecular-genetic analysis provides contemporary insights into the genotypic composition, circulation patterns, and evolutionary dynamics of the dominant NPEV associated with aseptic meningitis in the Ural Federal District and Western Siberia. The laboratory-based monitoring and epidemiological surveillance for genetic changes and evolutionary studies are important for improving prevention and healthcare. Full article
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11 pages, 2738 KB  
Article
Histopathologic and Genomic Characterization of a Novel Caprine Astrovirus Identified in a Boer Goat Kid in Illinois, United States
by Jingyi Li, Wes Baumgartner and Leyi Wang
Viruses 2026, 18(1), 120; https://doi.org/10.3390/v18010120 - 16 Jan 2026
Viewed by 445
Abstract
Astroviruses are non-enveloped, positive-sense single-stranded RNA viruses known to infect various mammals and birds, including humans, often causing gastrointestinal disorders. In recent years, astroviruses have also been linked to neurological and respiratory diseases across several species, including ruminants, mink, deer, and other mammals. [...] Read more.
Astroviruses are non-enveloped, positive-sense single-stranded RNA viruses known to infect various mammals and birds, including humans, often causing gastrointestinal disorders. In recent years, astroviruses have also been linked to neurological and respiratory diseases across several species, including ruminants, mink, deer, and other mammals. Notably, astrovirus infections in goats have been documented in countries such as Switzerland and China, where novel genotypes have been identified in fecal samples. However, their role in the context of disease remains unclear, and reports focusing solely on goat astrovirus in the United States have not been published. A necropsy case of a Boer goat kid with a history of diarrhea was submitted for investigation following death in January 2025. Fresh tissues were received and used for histopathology and enteric pathogen testing, including parasitic, bacterial, and viral workups. Metagenomic-based next-generation sequencing (mNGS) was also applied for this case. Histological examination revealed severe necrotizing enterocolitis. The small intestine exhibited epithelial ulcerations, villus atrophy, hyperplastic and dilated crypts with necrotic debris, few intraenterocytic coccidian parasites, and increased inflammatory cells in the lamina propria. The large intestine showed similar findings with pleomorphic crypt enterocytes. Standard enteric pathogen tests were negative except for aerobic culture that identified Escherichia.coli and Enterococcus hirae. mNGS and bioinformatic analysis identified a novel astrovirus in the intestinal content that showed the highest nucleotide identity (86%) to the sheep strain Mamastrovirus 13 sheep/HA3 from China based on BLAST analysis. Phylogenetic analysis indicated that the newly identified caprine astrovirus IL90175 clustered with astrovirus strains from small ruminants in Asia and Europe. This research reports the discovery, histopathologic features, and genetic characteristics of a gastrointestinal disease-causing astrovirus in a goat kid, which had not been previously described in the United States. Full article
(This article belongs to the Section Animal Viruses)
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