2026-11-30
Yunyueng Jang, Ra Mi Cha, Min-Ji Park, Jong-Min Kim, Eui Hyeon Lim, Gyeong-Beom Heo, Se-Hee An, Bina Lee, Hyun-Ji Seo, Kwang-Nyeong Lee, Youn-Jeong Lee, Eun-Kyoung Lee
ABSTRACT Clade 2.3.4.4b H5N1, H5N6, and H5N9 high pathogenicity avian influenza viruses (HPAIVs) were detected in poultry and wild birds during the 2025–2026 winter season in Korea. During this period, 62 H5Nx HPAI outbreaks occurred in poultry, and 63 cases were reported in wild birds. Genome constellation analysis revealed substantial genotype diversity. Most H5N1 and H5N9 genotypes were reassortants containing gene segments derived from East Asian clade 2.3.4.4b H5N1 HPAIVs since 2022 and low-pathogenicity avian influenza viruses from wild birds. Notably, the European H5N1 genotype EA-2024-DI.2.1, which spread rapidly across Europe in 2025, and its reassortants were identified in Korea. The novel poultry genotypes were also detected in wild birds, supporting wild bird to poultry spillover, whereas one genotype detected in previous season was identified in small-scale poultry farms. H5N1 (C588) of major 25G2 genotype in poultry and H5N9 (C722) of N9-G2 genotype showed high infectivity in chickens with 10 3.3 and 10 3.2 EID 50 of median lethal dose (LD 50 ) values, respectively. The predominance of the 25G2 genotype in poultry may have been influenced by efficient infection and virus introduction into high-density poultry production areas, potentially facilitating horizontal transmission under field conditions. In young ducks, H5N1 caused rapid mortality, whereas H5N9 induced limited clinical signs without mortality. Both viruses were transmitted to all contact ducks, increasing the risk of transmission to poultry. Despite intensified surveillance and early detection efforts to limit virus spread, H5Nx HPAIV outbreaks occurred during the 2025–2026 winter season. These findings highlight the need for continued surveillance, together with rapid genomic and pathogenic characterization of newly introduced viruses.
DOI: 10.1016/j.virusres.2026.1998072026-11-30
Md Abul Hashem, Mohammad Enamul Hoque Kayesh, Michinori Kohara, Kyoko Tsukiyama-Kohara
Hepatitis B virus (HBV) infection remains a major global health concern and is a leading cause of hepatocellular carcinoma (HCC). Despite advances in antiviral therapy and cancer treatment, HBV-related HCC (HBV-HCC) continues to pose significant challenges due to its complex pathogenesis involving chronic inflammation, viral persistence, and liver fibrosis. Current antiviral therapies reduce viral load and liver inflammation but often fail to eliminate integrated viral DNA or prevent carcinogenesis. On the other hand, cancer therapies such as surgery, ablation, immunotherapy, and targeted therapy have limited success when used in isolation, especially in patients with active HBV replication. This review examines the emerging concept of combining antiviral and anticancer strategies to improve clinical outcomes in HBV-HCC. We discuss the molecular mechanisms linking HBV infection to HCC, the role of antiviral therapy in reducing recurrence post-HCC treatment, and the impact of HBV reactivation during cancer therapy. In addition, we explore emerging biomarkers for early detection and prognosis, the therapeutic implications of HBV DNA integration, and the potential of gene-editing technologies targeting viral reservoirs. We further review the influence of HBV-induced immune dysregulation on immunotherapy outcomes, the relevance of host-microbiome interactions in liver carcinogenesis, and the utility of precision medicine approaches in guiding treatment. We highlight recent translational studies, clinical trials, and future directions that support a dual-modality approach, aiming for long-term remission and improved survival in patients with HBV-HCC.
DOI: 10.1016/j.virusres.2026.1998122026-11-30
Mostafizur Rahman, Md Ahad Ali, Tahosin Tasneem Samara, Monish Saha, Pritom Kundu, Hriddhi Sarker, Ankita Dutta, Neeraj Kumar
Infectious Myonecrosis Virus (IMNV) remains a major global threat to shrimp aquaculture, causing severe economic losses due to the lack of approved antiviral therapeutics. In this study, an advanced in silico approach was employed, utilizing a deep learning-based prediction of AlphaFold 3 protein structures and large-scale virtual screening of seaweed-derived metabolites to identify potential inhibitors targeting RNA-dependent RNA polymerase (RdRp). To identify potential seaweed-derived candidate compounds against IMNV, a total of 1077 compounds were screened against the RdRp_M01 protein. The docking results suggest the top-ranked three bioactive compounds, such as GA002 (-13.0 kcal/mol), RC003 (-10.9 kcal/mol), and BE012 (-10.8 kcal/mol), based on their highest binding energy score and molecular interactions, for further analysis. The 200 ns molecular dynamics simulations showed that the selected complexes exhibited stable behavior throughout the simulation time, with relatively low standard deviation values. Post-simulation MMGBSA analysis revealed total binding free energies (ΔG_total) of -24.726, -26.722, and -34.850 kcal/mol for RdRp_M01_GA002, RdRp_M01_RC003, and RdRp_M01_BE012, respectively, indicating favorable binding affinity and stable protein-ligand interactions. The drug-likeness and physicochemical profiles of the selected compounds were acceptable, supporting their further investigation. Therefore, further validation through in vitro and in vivo studies is necessary to confirm their applicability in shrimp systems and to explore the potential of seaweed metabolites as candidate compounds targeting the IMNV RdRp and alternatives to synthetic drugs.
DOI: 10.1016/j.virusres.2026.1997962026-11-30
Christina Wangen, Debora Obergfäll, Katarína Briestenská, Jela Mistríková, William D. Rawlinson, Manfred Marschall
Human herpesviruses represent major human pathogens. Members of the γ-Herpesvirinae subfamily are of particular interest because they cause chronic diseases, such as cancers, by altering cellular processes and driving resting cells into a continuously proliferating phase. Also, autoimmune diseases such as multiple sclerosis have continuously been in the focus of interest. The prototypic human γ-herpesvirus, Epstein-Barr virus (EBV), has proven difficult to analyze for the development of antiviral therapies due to challenges associated with propagating the virus in vitro, phenotyping it, and assessment of antiviral phenotypic efficacy. Similarly, developing experimental systems to study the second human pathogenic virus in this subfamily, Kaposi sarcoma-associated herpesvirus (KSHV), has been challenging. The murine γ-herpesvirus 68 (MHV-68) is a well-characterized homolog of EBV and KSHV and represents a model virus for cell culture-based and animal-specific analyses. Here, we used MHV-68 to determine virus sensitivity to antivirals, and combinatorial drug synergies. Much of the recent information about novel antiherpesviral drugs has come from studies of human cytomegalovirus (HCMV). Therefore, a comparative analysis was also conducted between HCMV, MHV-68, and EBV. The study demonstrated: (i) successful establishment of a new MHV-68 replication model in murine and non-murine cell types; (ii) optimization of an MHV-68-specific quantitative readout based on the luciferase reporter system; (iii) assessment of mechanistically novel antiherpesviral compounds; (iv) comparative antiviral effects spanning the three respective herpesviruses; (v) analysis of antiviral drug combination treatments able to identify statistically significant drug synergies. Overall, the study provides new insights into molecular aspects of γ-herpesvirus replication, as well as antiviral drug development and targeting strategies.
DOI: 10.1016/j.virusres.2026.1997992026-11-30
Lisa Arnold, Vanessa Schwarz, Gertrud Knoll, André Gessner, Barbara Schmidt, Markus Bauswein
Borna disease virus 1 (BoDV-1) is the causative agent of zoonotic infections resulting in severe encephalitis with a high case-fatality rate in humans. To search for an efficient in-vitro cell culture system for the generation of BoDV-1 virus stocks, we compared different human cell lines (A549, Caco-2, Calu-3, oligodendroglioma cells, SK-N-AS) and Vero cells with respect to BoDV-1 infection kinetics. While all cell lines included in the study supported the release of BoDV-1 RNA and its intracellular accumulation at the end of the experiment, viral RNA was detected in the supernatant of Calu-3 cells as early as six days post infection. In addition, two weeks post infection RNA loads remained highest in the supernatant of this cell line, which also yielded highest BoDV-1 RNA copies per cell. Using the ratio of BoDV-1 RNA in the supernatant and the cell pellet as a surrogate marker, Calu-3 cells released BoDV-1 RNA most efficiently. Notably, favipiravir (T-705), a drug with a described cell-type dependent inhibitory activity against BoDV-1 in vitro, which has been used as an off-label therapy in some cases of human BoDV-1 infection, did not reduce BoDV-1 RNA shedding into the supernatant of permanently infected Calu-3 cells and had only a limited effect in a de-novo infection model. In conclusion, our results underline the broad viral tropism of BoDV-1 in vitro and first describe a high release efficiency for BoDV-1 RNA in Calu-3 cells.
DOI: 10.1016/j.virusres.2026.1997952026-11-30
James O’Dwyer, Lachlan Coff, David Cummins, Peter G. Mohr, Nicholas J. Moody
Ostreid herpesvirus 1 (OsHV-1) is a major pathogen of Pacific oysters (Magallana gigas), linked to mass mortality events worldwide and presents a substantial threat to global aquaculture. Since 2010, mortality events have been occurring in Pacific oysters within Australia with the cause being an OsHV-1 microvariant highly similar to OsHV-1 μVar first detected in France, 2008. In this study, fifteen OsHV-1 whole genomes were assembled from Australian and New Zealand mortality events, including twelve newly sequenced genomes and three assembled from public datasets. Whole-genome phylogenetic analyses indicate that Australian and New Zealand OsHV-1 isolates form a distinct clade, separate from European and East Asian genomes, and with moderate regional and temporal divergence across the past 14 years. Across the dataset, multiple biologically relevant mutations were observed in genes of known function, including DNA polymerase, ribonucleotide reductase subunits, and apoptosis-related proteins, though most mutations occurred in uncharacterised genes. These findings highlight the limitations of single-gene typing and support the need for whole-genome approaches in understanding OsHV-1 evolution. Critically, the lack of recent whole-genome data, particularly from East and Southeast Asia, restricts the ability to trace viral origins and detect novel variants, underscoring the need for expanded global OsHV-1 genomic surveillance.
DOI: 10.1016/j.virusres.2026.1997982026-11-30
Shitian Huo, Pengfei Zhu, Jikai Xu, Kai Wang, Ming Sun, Donghai Peng
Aeromonas hydrophila is an opportunistic pathogen of fish, humans, and livestock, and has a severe negative impact on aquaculture development. Phage therapy is considered an alternative strategy for controlling bacterial infections and contamination. In this study, a novel phage, Aeromonas hydrophila BMBAH1, was isolated. Transmission electron microscopy showed that phage BMBAH1 had a long tail and an icosahedral head. Biological characterization indicated that phage BMBAH1 remained highly active across a broad range of temperatures and pH values, exhibiting long-term and significant inhibitory effects on host bacteria at an optimal multiplicity of infection (MOI) of 0.1. The genome of phage BMBAH1 is 237 kb in length with a guanine-cytosine (GC) content of 44.3%, and it was identified as a typical jumbo phage and predicted to contain 241 open reading frames (ORFs). Whole-proteome-based phylogenetic analysis, gene-sharing network analysis, and core protein clustering consistently indicated that phage BMBAH1 belongs to the family Chimalliviridae. However, phage BMBAH1 exhibited low intergenomic similarity to previously isolated phages, with values of approximately 30%. These results support the designation of phage BMBAH1 as the representative member of a candidate novel viral genus, designated Southlakevirus. Our findings expand the diversity of A. hydrophila phages and provide a promising genetic resource for further exploring biological characteristics of jumbo phages and developing biocontrol strategies.
DOI: 10.1016/j.virusres.2026.1998132026-11-30
Luciana Benevides, Herculano da Silva, Franciele Pioto, Thais da Silva Rigoni, Mariela Pires Cabral Piccin, Juliano de Paula Souza, Eurico Arruda, Vanessa Carregaro, João S. Silva
Zika virus (ZIKV) infection can cause severe neurological complications, particularly when antiviral immune responses are impaired. Here, we investigated how type I interferon (IFN-I) signaling influences the cellular inflammatory response and immunopathology in the central nervous system (CNS) during ZIKV infection. ZIKV infection induced early IFN-α and IFN-β expression in the CNS of wild-type (WT) mice. In contrast, mice lacking the IFN-I receptor (IFNAR -/- ) exhibited higher CNS viral loads, severe clinical symptoms, weight loss, increased mortality, and histopathological alterations characterized by extensive leukocyte accumulation and ZIKV antigen detection. Flow cytometry and UMAP analysis revealed that IFN-I signaling restrains leukocyte accumulation in the CNS. IFNAR -/- mice showed increased accumulation of myeloid and lymphoid cells, including inflammatory monocytes, monocyte-derived dendritic cells, and activated CD4 + and CD8 + T cells, whereas WT mice displayed limited leukocyte accumulation. Loss of IFN-I signaling was associated with elevated levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF, and IFN-γ), chemokines (CCL2, CCL4, and CCL5), and inducible nitric oxide synthase (iNOS). Notably, CNS-resident microglia from IFNAR -/- mice were highly susceptible to cell death, including among ZIKV antigen-negative cells, suggesting that inflammatory signals generated during infection may contribute to injury in uninfected microglia. In contrast, myeloid cells were predominantly ZIKV antigen-positive but remained largely viable. CD45 - non-leukocyte cells constituted the major ZIKV antigen-positive population in the CNS and displayed resistance to cell death, indicating that this compartment may represent an important cellular population associated with ZIKV antigen detection during acute infection. Together, these findings demonstrate that IFN-I signaling is essential for controlling ZIKV replication, restraining neuroinflammation, and limiting CNS immunopathology. Its absence leads to increased viral burden, dysregulated immune cell accumulation, and severe neurological disease.
DOI: 10.1016/j.virusres.2026.1998142026-11-30
Abid Ullah Shah, Csaba Varga, Nadine Moawad, Megan Rosen, Diane Levitan, Maged Gomaa Hemida
Feline Infectious Peritonitis Virus (FIPV) is a virulent biotype of feline coronavirus (FCoV) that causes fatal systemic disease in cats and continues to emerge through mutation and recombination. We conducted demographic data collection, molecular surveillance and genomic characterization of FCoV circulating in feral and shelter cats. Among 139 cats screened, 22.3% tested positive for FCoV. Lower weight and Body Condition Scores indicate higher likelihood for FCoV. Whole-genome sequencing identified three novel FCoV (FIPV-170, FIPV-193, and FIPV-246) belonging to FCoV type I. The viral genomes shared ≈90% nucleotide similarity among themselves and ≈83% similarity with local type II strains. Spike gene analysis revealed 76 amino acid substitutions in the S1 region, including 12 mutations in the receptor-binding domain. Accessory gene mutations included a premature stop codon in NSP-3a and truncation of NSP-7a. Recombination analysis identified mosaic genomes derived from feline coronavirus types I and II and canine coronavirus lineages, with breakpoints in ORF1b, spike, and NSP-3abc regions, resembling patterns reported during the recent 2023 FCoV outbreak in Cyprus (FCoV-23). Continued regional molecular and genomic surveillance is advised.
DOI: 10.1016/j.virusres.2026.1998022026-11-30
Kentaro Uemura, Shinsuke Toba, Shinji Kusakabe, Michihito Sasaki, Yasuko Orba, Naoyoshi Maeda, Mayumi Ishii, Kayoko Kanamitsu, Hirofumi Sawa, Akira Matsuda, Akihiko Sato, Katsumi Maenaka
Several newly emerging and re-emerging viral infections significantly affect human health and the global economy each year. As many of these viruses lack treatment options other than symptomatic management, the development of effective preventive and therapeutic measures is urgently needed. We previously identified 5-hydroxymethyltubercidin (HMTU) as a broad-spectrum antiviral ribonucleoside analog and demonstrated its in vitro potent antiviral activity against positive-sense single-stranded RNA viruses, including dengue virus (DENV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we evaluated the in vivo efficacy, pharmacokinetics, and safety of HMTU. Pharmacokinetic analysis revealed that effective concentrations of HMTU were maintained in the plasma and lung tissues of mice following intravenous and intramuscular administration. In a DENV2 infection model using AG129 mice, prophylactic administration of HMTU provided 100% protection against lethal infection. Similarly, in a SARS-CoV-2 infection model using BALB/c mice, HMTU significantly reduced viral titers in the lungs and improved the survival rates versus those in vehicle-treated mice. Furthermore, mutagenicity assessments using the Ames and HPRT tests demonstrated that HMTU did not exhibit mutagenic activity under the tested conditions. Our findings highlight HMTU as a broad-spectrum antiviral candidate potentially offering a promising therapeutic approach for dengue, COVID-19, and other infectious diseases caused by emerging orthoflaviviruses and coronaviruses.
DOI: 10.1016/j.virusres.2026.1998172026-11-30
Kehinde A. Oyeniran, Temilola Aina, Lara Donaldson
The A-strain maize streak virus (MSV-A; genus Mastrevirus, family Geminiviridae) is a single-stranded DNA (ssDNA) virus that severely constrains the production of maize in sub-Saharan Africa and other places where its insect vectors thrive. In this review, we discuss the ecology- and genomics-driven evolution of this economically important virus and strategies targeting streak resistance in maize. Evolution of MSV-A is largely driven by the interplay of mutation, recombination and selective forces that may sustain fitness and result in host adaptation. In the last decade, research efforts, including fine-mapping of quantitative trait loci (QTL), gene pyramiding, clustered regularly interspaced short palindromic repeats (CRISPR) techniques, microRNA gene silencing and farming practices, have had key roles in creating maize genotypes that are resistant to streak diseases caused by MSV-A and other plant-infecting viruses. However, these techniques may also foster the rapid emergence of editing-resistant variants, requiring more thorough and rigorous validations for desired results. We propose a five-cardinal agenda for future research covering layered surveillance-supported host resistance, evolutionary surveillance, agro-ecological alignment of breeding, escape-aware editing stewardship and policy harmonisation. Moreover, the in-depth understanding of the interplay between pathogens, hosts, and biotic interventions for breeding resistance is central to achieving crop improvement, agricultural productivity, and food security.
DOI: 10.1016/j.virusres.2026.1998102026-11-30
Federico Romiti, Silvia Tofani, Antonella Cersini, Irene Del Lesto, Maria Teresa Scicluna, Gaetana Anita Marcario, Davide La Rocca, Silvia Rondón, Adele Magliano, Claudio De Liberato
Tahyna virus (TAHV) is a neglected mosquito-borne Orthobunyavirus pathogenic to humans. In Italy, TAHV was first recorded in Friuli Venezia-Giulia and then repeatedly in Emilia Romagna Region (Northern Italy). This study was set up to verify the presence of TAHV in Central Italy and to identify its potential vectors. Mosquito surveillance was conducted from April to November 2025, using 78 CDCCO₂ traps across Latium and Tuscany Regions. A total of 17,728 Culicidae was captured, including 9237 specimens of four potential vector Aedes species (Aedes albopictus, Aedes caspius, Aedes detritus, and Aedes vexans). Aedes caspius was the dominant species, showing a marked abundance peak from late-summer to early-autumn. Additionally, a high density of Ae. vexans, a primary TAHV vector species in Europe, was recorded in Arezzo province, Eastern Tuscany. A total of 356 pools of the Aedes species, made up of 6600 specimens, was screened for TAHV by real-time and conventional PCR. TAHV was detected in one pool of Ae. caspius collected in Grosseto province, Southern Tuscany. This study provides the first report of TAHV in Central Italy, identifying the southernmost detection in the Country to date.
DOI: 10.1016/j.virusres.2026.1998152026-11-30
Rapeepat Tippayawong, Wiratchanee Kansandee, Chaleampol Loymunkong, Padtaya Sirinantananon, Sirirat Mahawan, Kans Suwanmali, Nattarpart Lookluck, Chamsai Pientong, Tipaya Ekalaksananan, Jureeporn Chuerduangphui
Herpes simplex virus (HSV) and human papillomavirus (HPV) infections remain major global health concerns, particularly in immunocompromised individuals. Herbal extracts have emerged as promising candidates for developing novel antiviral agents, particularly against drug-resistant viruses. This study examined the inhibitory effects of Polyscias scutellaria (Burm.f.) Fosberg, a tropical ornamental plant with edible young shoots and leaves against HSV, HPV, and cervical cancer cell growth. Four extracts prepared from fresh and dried leaves using ethanolic and hot-water methods were evaluated for their inhibitory activities against drug-susceptible and drug-resistant HSV and HPV, as well as for their effects on CaSki and HeLa cell growth, using plaque inhibition, HPV-16 pseudovirus binding, wound-healing, acridine/ethidium dual staining, and flow cytometry assays. Gene and protein expression levels were analyzed by quantitative qPCR and western blot analysis. The ethanolic extract of fresh P. scutellaria exhibited the strongest inhibitory effects against both wild-type and drug-resistant HSV strains among all extracts tested and downregulated HSV-1 ICP4, UL30, US6 and gC. This extract also suppressed HPV-16 pseudovirus infection at an early stage. In addition, it reduced cancer cell proliferation and increased apoptosis, while suppressing HPV-16/18 E6, BCL2, and NFKB1 expression and upregulating BAX expression. The putatively annotated metabolites with the highest peak area in P. scutellaria, identified using electrospray ionization-quadrupole time-of-flight mass spectrometry, showed favorable drug-likeness and potential interactions with candidate HSV-1 and HPV-16 proteins based on in silico analysis. Notably, a prototype herbal soap containing this extract significantly reduced drug-resistant HSV-1 infection and HPV-16/18 E6 expression. These findings highlight P. scutellaria as a promising natural antiviral and anticancer agent with potential for health-product development.
DOI: 10.1016/j.virusres.2026.1998082026-11-30
Maryam Mashhadi Abolghasem Shirazi, Ochilova Dilorom, Shamuratova Gulnora Baxtiyorovna, Aseel Smerat
Zoonotic viral spillover represents a major global health challenge arising from complex interactions among viral evolution, reservoir ecology, host biology, environmental disruption, and human activities. Successful emergence requires viruses to overcome successive ecological, cellular, and immunological barriers, including receptor compatibility, cellular tropism, replication efficiency, and innate immune restriction. Reservoir hosts such as bats, rodents, birds, and livestock contribute to viral maintenance and diversification through distinct ecological and physiological characteristics, while deforestation, agricultural expansion, wildlife trade, intensive farming, urbanization, and climate variability can increase opportunities for cross-species transmission. Following spillover, viral adaptation and host susceptibility determine whether infections remain sporadic or progress to sustained human transmission. This review integrates ecological, molecular, immunological, and anthropogenic determinants of zoonotic emergence and examines major historical spillover events involving coronaviruses, influenza viruses, filoviruses, henipaviruses, and arboviruses. We further evaluate genomic and metagenomic surveillance, wastewater monitoring, artificial intelligence, ecological modeling, and integrated One Health approaches for early risk assessment and pandemic preparedness. Major knowledge gaps include limited characterization of global viral diversity, surveillance bias, inadequate functional validation of newly identified viruses, fragmented data systems, and limited predictive capacity. Future prevention requires integration of technological innovation with ecological conservation, equitable surveillance capacity, responsible biotechnology governance, and sustainable One Health Planetary Health strategies.
DOI: 10.1016/j.virusres.2026.1998182026-11-30
Sara Passerini, Maria Dolci, Sara Messina, Valentina Alyssa Caterina, Lucia Signorini, Francesca Camurri, Marco Graziani, Giorgia Gallo, Giovanni Di Nardo, Serena Delbue, Valeria Pietropaolo
Merkel cell polyomavirus (MCPyV) is the established oncogenic driver of Merkel cell carcinoma (MCC), but its role in other malignancies is under investigation. Although MCPyV DNA has been detected in colorectal cancer (CRC) specimens, its biological relevance and contribution to colorectal tumorigenesis remain unclear. In this observational study, we investigated MCPyV prevalence, load and molecular status in 122 CRC specimens and peritumoral tissues. In addition, to extend beyond DNA detection, transcriptional profiling was performed to assess early (LTAg) and late (VP1) transcripts, and viral microRNAs. Furthermore, the mRNA expression levels of key Wnt signaling components, including CTNNB1, MYC and CCND1 were examined. AXIN2 was also used as a surrogate marker of pathway activation. Our findings revealed similar MCPyV prevalence and load between tumor and adjacent healthy tissues, suggesting a wide colonization of the colorectal mucosa. Sequencing analyses showed canonical NCCR and VP1 structures, and full length LTAg, with no evidence of viral integration. These data, combined with the detection of both early and late transcripts, indicate an episomal and transcriptionally active state in colorectal tissues. Notably, virus-positive tissues exhibited an over-expression of CTNNB1and its target genes across all clinical subgroups, regardless of anatomical site or tumor stage. Our results are congruent with the establishment of persistent MCPyV infection in the colorectal mucosa, potentially characterized by transcriptionally active episomal genomes. Furthermore, upregulation of the Wnt/β-catenin cascade in virus-positive tissues suggests that MCPyV may exploit this host pathway to drive cellular proliferation. A limitation of this study is lack of comparison to colorectal mucosa in patients without CRC. Overall, these findings are consistent with widespread viral colonization of the colorectal mucosa in a subset of CRC patients, and raise the hypothesis that MCPyV may modulate host signaling pathways relevant to colorectal biology. Whether MCPyV plays any etiological role in colorectal carcinogenesis, or whether its detection is coincidental, cannot be determined from the present observational data.
DOI: 10.1016/j.virusres.2026.1998092026-11-30
Evangelia Georgia Kostaki, Stefanos Limnaios, Georgios Adamis, Georgios Xylomenos, Maria Chini, Nikos Mangafas, Marios Lazanas, Stavros Patrinos, Simeon Metallidis, Olga Tsachouridou, Vasileios Papastamopoulos, Dimitrios Chatzidimitriou, Anastasia Antoniadou, Antonios Papadopoulos, Konstantinos Protopapas, Chrysa Tsiara, Mina Psichogiou, Dimitrios Basoulis, Dimitrios Pilalas, Dimitra Paraskeva
Late presentation remains a major hurdle for HIV management and prevention. We investigated the potential source of transmission among people living with HIV (PLHIV) with different stages of diagnosis, using a combined approach of the traditional definition of late presentation (CD4-based) and the estimated time between HIV acquisition and diagnosis. The study included 3,093 HIV-1 subtype A1 and B sequences from a period with dense sampling in Greece. HIV acquisition dates were estimated using molecular clock analysis and transmissions patterns were assessed with a modified phylogeographic approach. For subtype A1, analysis using the estimated time from HIV acquisition to diagnosis revealed that among PLHIV with recent diagnosis, the mean number of infections originating from PLHIV with late and intermediate diagnosis, were 35.7 (11%) and 32.8 (10.2%), respectively. For those diagnosed late, 21.3 (6.7%) and 18.5 (5.8%) infections (mean number) were from PLHIV with intermediate and recent diagnosis, respectively. Similarly for subtype B, a considerable proportion of infections among PLHIV with recent (12.2%) and intermediate (13.1%) diagnoses originated from PLHIV with late status. Statistical phylogeography confirmed that late presenters were a significant source of transmission to PLHIV in other diagnosis-status categories for both subtypes. Analysis using CD4 cell count showed that late presentation and advanced disease groups provided a significant source of transmission to other groups. Our study highlights that early diagnosis, besides the beneficial effect for the disease prognosis, would significantly mitigate onward HIV transmission. This underscores the need to enhance HIV testing strategies in Greece to ensure earlier diagnosis and timely treatment initiation.
DOI: 10.1016/j.virusres.2026.1998032026-11-30
Ya-ting Zheng, Xian-zhu Jin, Chuan-jian Zhang, Sai-sai Chen, Nikolaus Osterrieder, Ya-mei Liu, Ji-chun Wang
BACKGROUND: Pseudorabies virus (PRV) variants have emerged as major swine pathogens associated with high piglet mortality and reproductive losses in China since 2011. Conventional oil-adjuvant vaccines are effective but frequently induce adverse local reactions. Water-soluble adjuvants, such as the nano-adjuvant IMS 1313, confer improved safety and potent immunogenicity. This study aimed to develop an inactivated PRV vaccine based on IMS 1313 combined with an immunopotentiator and evaluate its immune protective efficacy. METHODS: Multiple adjuvant-immunopotentiator combinations were screened. The PRV LA1206-80 strain formulated with IMS 1313 plus immunopotentiator c exhibited the optimal comprehensive performance and was selected for subsequent evaluation. Mice were immunized to detect serum neutralizing antibody titers and survival-based protection rates. Piglets were immunized via intramuscular or intradermal routes, and immune responses, post-challenge viral shedding, as well as histopathological lesions were monitored. Oil-adjuvant inactivated vaccine and live attenuated vaccine were set as control groups. Virus neutralization assays were performed to determine neutralizing antibody responses. RESULTS: After two immunizations with a 28-day interval, the IMS 1313 + immunopotentiator c formulation induced a neutralizing antibody titer of 1:32 and achieved 93.3 % protection in mice, which was markedly higher than that of the control groups (1:5.6). In this preliminary exploratory piglet trial, intramuscular vaccination yielded peak neutralizing antibody titers of 1:295.8, which appeared higher than those of the oil‑adjuvant vaccine (1:28.2) and live vaccine (1:13.1). This immunization regimen achieved 100 % survival, accompanied by reduced viral shedding and minimal pathological lesions. Intradermal vaccination conferred relatively lower protective efficacy, underscoring the critical influence of immunization route. CONCLUSION: IMS 1313 combined with immunopotentiator c markedly enhances the immunogenicity and safety profile of inactivated PRV vaccines in mice. Preliminary data from piglets revealed favourable protective trends upon intramuscular vaccination. This candidate represents a promising safer alternative compared with conventional oil-adjuvant vaccines and warrants further larger-scale efficacy evaluation.
DOI: 10.1016/j.virusres.2026.1998012026-11-30
Garvit Kumar, Assim Verma, Shweta Dhanda, Himanshu Kamboj, Riyesh Thachamvally, Shoor Vir Singh, Ram Kumar, Naveen Kumar
In this study, we demonstrate that activation of PPARγ (Peroxisome Proliferator-Activated Receptor Gamma), a nuclear receptor and transcription factor, by its agonist Rosiglitazone significantly suppresses replication of Buffalopox virus (BPXV). Time-of-addition and step-specific assays revealed that rosiglitazone primarily inhibits viral genome replication and protein synthesis, while showing no measurable effect on viral attachment, entry, or release in infected cells. Mechanistic investigations identified miR-27a, an endogenous negative regulator of PPARγ, as a proviral factor displaying an inverse expression pattern with PPARγ during infection. At 12 h post-infection, corresponding to the peak of viral mRNA translation, miR-27a expression was maximal whereas PPARγ levels were markedly reduced, suggesting a critical regulatory axis controlling viral translation. Activation of PPARγ suppressed the p38α MAPK-MNK1-eIF4E signaling pathway required for cap-dependent viral mRNA translation. Notably, the antiviral effect of rosiglitazone was abolished in p38α-knockout cells, confirming the involvement of p38α signaling. Although PPARγ did not directly interact with p38α, it induced the expression of DUSP1, a known negative regulator of p38α activity. Pharmacological inhibition of DUSP1 restored viral replication in rosiglitazone-treated cells, supporting a PPARγ-DUSP1-mediated mechanism. Furthermore, rosiglitazone significantly reduced BPXV-induced mortality and pock lesion formation on the chorioallantoic membrane of specific pathogen-free embryonated chicken eggs. Importantly, prolonged viral passage in the presence of the inhibitor did not lead to the emergence of resistant variants, underscoring the potential of rosiglitazone as a host-directed antiviral strategy with a low likelihood of inducing antiviral resistance.
DOI: 10.1016/j.virusres.2026.1998112026-11-30
Essowè Palanga, Agnès Pinel-Galzi, Denis Filloux, Adeline Pinault, Kossi Essotina Kpemoua, Essohouna Ali, Charlotte Julian, Damien Richard, Nils Poulicard, Philippe Roumagnac, Eugénie Hébrard
Maize yellow mosaic virus (MaYMV) (Polerovirus MAYMV, Solemoviridae) is an emerging virus with a global distribution in maize and other cereals. Transmitted by aphids in a circulative, non-propagative manner, MaYMV forms icosahedral particles and possesses a positive-sense, single-stranded RNA genome. Three distinct phylogenetic groups of MaYMV have been described in Asia, East Africa and America. In this study, 19 genomes from Togo and Burkina Faso were sequenced using Virion-Associated Nucleic Acid-Based Metagenomics (VANA) combined with classical RT-PCR to constitute the first dataset of West African MaYMV genomic sequences. Phylogenetic analyses of global dataset of 92 genomic sequences revealed two sub-lineages within the African strain. We also identified 11 recombinant MaYMV genomes involving intra- and inter-continental exchanges. A comparative analysis of non-recombinant sequences was conducted and identified 19 molecular signatures in proteins P0, P1, P4 and P5. Notably, residue K/R 253 in P5 was lineage-specific and is located near conserved polero- and luteovirus residues known to be involved in aphid interactions, suggesting a potential role in viral transmission.
DOI: 10.1016/j.virusres.2026.1998042026-11-30
Meareg G. Amare, Peter J. Halfmann
Ebola virus disease is a severe illness with high mortality for which limited therapeutic options are available. Identifying new antiviral drugs that target viral proteins is essential for improving prevention and treatment strategies. In this study, we screened a library of 2,620 small molecules enriched for reported inhibitory activity against cellular and viral helicases to identify phenotypic inhibitors of a biologically contained virus, Ebola∆VP30 virus, in Vero cells stably expressing VP30 protein. Seven compounds significantly reduced virus titers at least 100-fold with minimal cytotoxicity and demonstrated low IC 50 values. Two of these compounds completely inhibited EbolaΔVP30 virus infection, interfering with either virus entry or replication. Although these preliminary screening hits require further optimization and in vivo validation, their identification opens new avenues for anti-Ebola virus drug discovery.
DOI: 10.1016/j.virusres.2026.1998232026-11-30
Narinderjit Singh Sawaran Singh, Murtaja Satea, Ali Jawad Kadhum, Ibrahm Mahariq, Hemn A.H. Barzani, Baydaa Abed Hussein, Mina D. Jumaah, Mahmut Taner, Soheil Salahshour, A. Rahimi
Capturing nanoscale biological objects in nanochannels depends strongly on surface geometry and interfacial interactions. However, the spatial and temporal limitations of atomistic simulations prevent the direct representation of a complete rabies virion. In this study, we used molecular dynamics simulations to examine the force-driven retention of a reduced rabies-virus model with a characteristic size of approximately 4 nm in a water-filled platinum nanochannel with non-ideal surface roughness. The simulated construct was developed from reported rabies-virus structural information but did not reproduce the complete morphology, envelope, genomic content, or biological functionality of an intact virion. The atomic interactions were described using DREIDING and Universal Force Field parameters, the TIP3P water model, the embedded atom method for Pt-Pt interactions, and Lennard-Jones and Coulombic terms for interfacial interactions. After 10 ns of canonical equilibration at 300 K, the system underwent a 20 ns force-driven production stage. Roughness sizes of 35, 37, 40, and 43 Å were investigated. Among the four simulated configurations, the 40 Å roughness case produced the largest maximum density (0.187 atom/ų), the lowest maximum velocity (0.006 Å/ps), the largest retained surface-mesh volume (31,118 ų), and the most negative reduced-model-Pt interaction energy (-469.91 kcal/mol). The simulation-defined retained fraction for the reduced construct reached 95% at 20 ns. The weaker responses at 43 Å indicated a non-monotonic dependence on roughness size within this model and the investigated geometries. These results characterized the force-driven behavior of a specific 4-nm construct under the stated simulation conditions; they did not establish roughness-dependent capture behavior for intact rabies virions or predict experimental device performance.
DOI: 10.1016/j.virusres.2026.1998162026-11-30
Mohamad Reza Choobineh, Daryoosh Choobineh, Behzad Hajieghrari
MicroRNAs (miRNAs) are small non-coding RNA molecules, approximately 22 nucleotides in length, that regulate post-transcriptional gene expression and have emerged as pivotal modulators of host-virus interactions. Veterinary viral diseases continue to pose substantial challenges to animal health, livestock productivity, food security, and public health, particularly due to their zoonotic potential. While miRNA research has advanced considerably, a comprehensive and critically integrated understanding of their biological functions and clinical applications across veterinary viral diseases remains incomplete. This comprehensive critical narrative synthesis addresses four overarching research questions: (1) What conserved and species-specific miRNA-mediated mechanisms govern major veterinary viral diseases? (2) What contextual factors determine antiviral vs. proviral duality? (3) To what extent do circulating miRNA signatures offer diagnostic and prognostic utility? (4) What translational barriers currently prevent clinical implementation, and how can the One Health framework help overcome them? Integrating three interconnected dimensions-molecular mechanisms, pathogen-specific responses, and translational applications-the review synthesizes evidence across PRRSV, avian oncogenic viruses (MDV, ALV), the immunosuppressive IBDV, FMD, BVDV, Ebola, Hendra, Rabies, and aquatic viral diseases. A key contribution of this review is the proposal of a four-axis contextual framework that explains the antiviral/proviral duality of miRNAs, and a 'One miRNA, One Health' convergence model with a concrete implementation roadmap. Key findings include: (a) a four-axis contextual framework (cell type, infection stage, viral strain, host-viral miRNA competition) that explains the antiviral/proviral duality; (b) virus-encoded miRNAs (v-miRNAs) as lower-risk therapeutic targets due to their absence from uninfected host genomes; (c) circulating miRNA biomarkers validated only at proof-of-concept stage (TRL 1-3), with no veterinary product yet at TRL ≥4; and (d) zoonotic conservation of miR-155, miR-146a, miR-21, and miR-122 across human and veterinary pathogens, supporting a 'One miRNA, One Health' convergence strategy. Critical short-term priorities are standardized pre-analytical protocols, open-access veterinary miRNA databases, and multicenter validation in natural infection cohorts.
DOI: 10.1016/j.virusres.2026.1998002026-11-30
Wantana Maneesriwongul, Suhong Deesamer, Nipaporn Butsing
BACKGROUND: Parental acceptance plays an important role in childhood COVID-19 vaccination, but factors underlying vaccine acceptance in Thailand remain insufficiently understood. This study assessed parents' vaccine attitudes, beliefs, preference to choose, willingness to pay for COVID-19 vaccine, and children's past influenza vaccination and examined their influence on COVID-19 vaccine acceptance for their children aged 6 months to <10 years. METHODS: An online cross-sectional study was conducted in Thailand. A sample of 973 Thai parents with children aged 6 months to <10 years was used for data analysis using multivariate multinomial logistic regression. RESULTS: Results showed that 98.6% of parents reported receiving COVID-19 vaccination, but only 51.3% would accept COVID-19 vaccine for their children. Univariate multinomial logistic regression analyses showed that parent's age, trust in health professionals, beliefs in COVID-19 vaccine safety, opinions that children should also be vaccinated, negative attitudes about vaccination, willingness to pay for the vaccines, and children's age were associated with parents' COVID-19 vaccine acceptance for their children. The final multivariate model included children's age, beliefs in vaccine safety, trust in health professionals, opinions that children should also be vaccinated, negative attitudes about vaccination, and willingness to pay for the vaccines. Although the children's past influenza vaccination showed a significant association with parents' COVID-19 vaccine acceptance for their children in univariate analysis, it was not retained in the multivariate multinomial logistic regression model. CONCLUSIONS: Parents should receive vital information from health professionals about the safety of the COVID-19 vaccination to increase its acceptance for children. The results will benefit future planning for vaccination programs for children when both the COVID-19 vaccine and annual influenza vaccine are recommended as essential immunizations for children.
DOI: 10.1016/j.virusres.2026.1998052026-11-30
Yuxin Zhao, Haitian Fan
Background Seasonal influenza imposes substantial clinical and economic burdens, with pediatric populations facing escalating risks of severe complications. While baloxavir marboxil (baloxavir) is an efficacious cap-dependent endonuclease inhibitor, the emergence of treatment-induced PA I38T/M substitutions has raised critical public health concerns. This study aimed to quantify the incidence and clinical consequences of these mutations across diverse populations and explore their mechanistic basis through structural modeling. Methods A systematic review and meta-analysis of prospective clinical trials was conducted. Primary outcomes included the pooled incidence of mutations and the time to illness alleviation (TTIA). Leave-one-out sensitivity analyses and structural modeling were integrated to evaluate robustness and potential mechanisms. Results Five prospective clinical trials comprising pediatric, uncomplicated, and high-risk adult patients were included. The pooled incidence of PA substitutions was 10.5% (95% CI: 0.0% to 21.1%; I 2 = 94.6%). While the overall pooled incidence was robust, the highest mutation rates (up to 23.4%) were disproportionately observed in pediatric cohorts. Overall pooled analysis showed a numerical but statistically non-significant 15.47-hour delay in TTIA (95% CI: -40.96 to 71.91; P = 0.359; I 2 = 81.8%). However, subgroup analysis revealed this overall non-significance was an artifact of stark demographic divergence: the mutant-induced TTIA prolongation showed a modest numerical increase of 5.67 hours in adults, whereas this gap widened to 36.8 hours in the pediatric cohort. Furthermore, PA substitutions extended the median duration of infectious viral shedding from 24.0 to 180.0 hours in pediatric patients. Conclusions PA I38T/M substitutions are associated with noteworthy virological rebound and delayed clinical recovery, predominantly in pediatric populations. These findings emphasize the requirement for age-specific resistance monitoring and support the evaluation of combination antiviral therapies to mitigate resistance emergence.
DOI: 10.1016/j.virusres.2026.1997972026-10-31
Aziz Ul-Rahman, Muhammad Zubair Shabbir, Muhammad Munir
Newcastle disease virus (NDV) remains one of the most economically important avian pathogens worldwide, causing recurrent outbreaks in poultry despite decades of vaccination and disease control efforts. Since the first reported outbreak of NDV a hundred years ago, numerous molecular epidemiological studies have been conducted globally across diverse geographic and production settings. Following a century of NDV circulation and evolution, the present study aimed to compile all publicly available NDV sequence data and perform a comprehensive global analysis of the genetic diversity, phylogenetic relationship, and global spatiotemporal distribution of NDV over a 100-year timescale. All publicly available NDV complete genome and full-length fusion (F) gene sequences were retrieved from GenBank up to February 2026. Following rigorous quality control, phylogenetic analyses were performed based on complete genomes and F gene datasets. Phylogenetic analysis identified two genotypes within Class I and 20 genotypes within Class II NDVs, with extensive diversification at the sub-genotype level. Genotype XIII exhibited the greatest sub-genotypic diversity, while genotype VII represented the most globally disseminated genotype, reported across 36 countries. Chronological assessment based on the earliest available reports indicated an increasing number of recognized genotypes from the 1930s to recently described sub-genotypes such as XIII.2.3 and XXII.2.2. Regional diversity analysis revealed the highest genotype diversity in Western Africa, Eastern Asia, and Southern Asia. Comparative residue analysis demonstrated substantial genotype-specific variation within critical functional domains of the fusion protein, including cleavage sites, neutralizing epitopes, and heptad repeat regions. Overall, this study provides the first comprehensive 100-year global overview of NDV evolution and phylogeography. The findings highlight continuous viral diversification, broad geographic dissemination of multiple genotypes, and ongoing molecular variation, emphasizing the need for sustained genomic surveillance and periodic evaluation of vaccine compatibility with emerging NDV genotypes.
DOI: 10.1016/j.virusres.2026.1997832026-10-31
Jun Young Lee, Jung-ah Choi, Dae-Im Jung, Yunjeong Park, Eunji Yang, Chanmi Kim, Minkyung Ko, Seung Ho Baek, Jung Joo Hong, Soon-Hwan Kwon, Won-Tae Kim, Manki Song, Sang Hwan Seo
Human adenovirus type 55 (HAdV-55) is an emerging respiratory pathogen associated with severe pneumonia and acute respiratory disease, yet no licensed vaccine is currently available. Here, we evaluated the immunogenicity and protective efficacy of an inactivated HAdV-55 vaccine formulated with aluminum hydroxide (iHAdV-55 + AH) in cynomolgus macaques. Animals received a prime–boost intramuscular immunization, and HAdV-55-specific binding IgG and neutralizing antibody responses were monitored longitudinally for up to 52 weeks. Protective efficacy was assessed in two independent respiratory challenge studies using combined intranasal and intratracheal inoculation with either a high dose (1 × 10 11 plaque forming unit: PFU) or a low dose (1 × 10 9 PFU) of HAdV-55. Vaccination induced HAdV-55-specific binding and neutralizing antibody responses that remained detectable throughout the 52-week study period. Following the high-dose challenge, vaccinated macaques showed reduced pulmonary lesion burden on chest computed tomography, lower relative lung weights, and attenuated histopathological changes compared with PBS controls. In the low-dose challenge model, where overall disease manifestations were milder, vaccinated animals consistently exhibited fewer radiologic abnormalities, reduced inflammatory cell infiltration, and decreased viral shedding in nasal swabs. No evidence of vaccine-enhanced respiratory disease was observed in either challenge setting. Together, these findings indicate that iHAdV-55 + AH is immunogenic and attenuates HAdV-55-induced pulmonary pathology in this non-human primate model, supporting further development of inactivated vaccine strategies against severe HAdV-55 infection.
DOI: 10.1016/j.virusres.2026.1997932026-10-31
Kangyixin Sun, Li Li, Jia Yang, Fuqiang Xu, Fan Jia
Vesicular stomatitis virus (VSV) -ΔG vector particles are widely applied in vaccine development, gene delivery, and immunotherapy studies due to their high transduction efficiency and replication-defective design. However, G-pseudotyped VSV-ΔG preparations may exhibit residual multicycle infectivity associated with VSV-G-dependent entry. Therefore, in this study, we generated VSV-ΔG particles and corresponding M51R and ΔM51 derivatives to examine the relationship between G-dependent residual infectivity and post-entry innate immune regulation. Serial passage experiments were performed with removal of the inoculum and repeated PBS washing, followed by RT-PCR and Sanger sequencing of viral genomic regions. Detectable infectivity persisted transiently during early passages but progressively declined, while no evidence of restoration of the deleted VSV-G gene was identified. Neutralization with anti-VSV-G antibody markedly reduced infection, supporting the dependence of the observed residual infectivity on functional VSV-G-mediated entry. M51 mutations were associated with enhanced interferon-related signaling after infection. Together, these findings distinguish limited G-dependent residual infectivity from restoration of replication competence and highlight the need to consider such activity during the characterization and interpretation of G-pseudotyped VSV-ΔG systems.
DOI: 10.1016/j.virusres.2026.1997922026-10-31
Bijan Godarzi, Cora M. Holicki, Felicity D. Chandler, Anne van der Linden, Reina S. Sikkema, Edwin J.A. Veldhuizen, Aart van Amerongen, Andrea Gröne
Usutu virus (USUV) is an arbovirus that circulates between mosquitoes and birds with occasional spillover events into non-avian species. USUV continues to circulate in the Netherlands, particularly in Eurasian blackbirds (Turdus merula), although other USUV-susceptible avian species have also been found. Current serosurveillance systems make use of serological methods that can detect anti-USUV antibodies in sera collected from live birds. However, they require a dedicated laboratory and rarely include serological analysis of deceased avian specimens. As a proof of concept, this study evaluates the use of a previously developed lateral flow microarray immunoassay (LMIA) to detect USUV non-structural 1 (NS1)-specific antibodies in blood clots and lung and liver tissue extracts collected from blackbird carcasses found in the Netherlands. The likelihood of detection of USUV NS1 antibodies in USUV RT-PCR-positive blackbirds was found to trend higher in lung tissue extracts. Additionally, the LMIA exhibited only minimal cross-reactivity between USUV NS1-specific antibodies and USUV NS1 and West Nile virus (WNV) NS1 capture antigens on the LMIA. This initial study demonstrates the feasibility of the LMIA to specifically detect USUV NS1 antibodies in lung tissue extracts of deceased blackbirds. In future, a serological tool such as the one presented here, would allow for the rapid on-site analysis of both live and deceased blackbird specimens found in the field.
DOI: 10.1016/j.virusres.2026.1997892026-10-31
Xueqi Li, Zhenye Niu, Tangwei Mou, Yang Gao, Lichun Wang, Ying Zhang, Huan Chen, Shubo Tan, Jia Liu, Jianjun Li, Qihan Li
Rabies virus (RABV) is a zoonotic pathogen with an almost 100% case-fatality rate and limited post-exposure prophylaxis options. mRNA-based antigen delivery represents a promising approach but requires further optimization. We prepared a cationic lipid nanoparticle (LNP) delivery system using the thin-film hydration method and characterized its physicochemical properties and delivery efficiency. An mRNA encoding a fusion antigen comprising rabies virus glycoprotein (G) and herpes simplex virus type 2 infected cell polypeptide 35 (ICP35), lacking canonical 5' and 3' untranslated region sequences, was constructed. In vitro protein expression of the G-ICP35 mRNA was confirmed. Immunogenicity was evaluated in BALB/c mice following three intramuscular immunizations with G-ICP35 mRNA, RABV G/N proteins, or their combination. Tail vein blood samples were collected on days 7, 21, and 39 after the final immunization, and rabies virus-specific antibody titers and T-cell responses were assessed. The cationic LNP formulation efficiently mediated intracellular delivery and expression of the G-ICP35 mRNA. In vivo, the mRNA-LNP formulation induced detectable humoral and cellular immune responses, including rabies virus-specific IgG production and antigen-specific T-cell activation. Notably, co-immunization with mRNA and subunit vaccines further enhanced immune responses compared with either vaccine alone, achieving peak rabies virus-specific IgG titers of 694.5 IU/mL. These findings demonstrate the feasibility of a DCChol-based mRNA-LNP formulation for fusion antigen delivery and support further investigation of combined mRNA and subunit vaccine strategies.
DOI: 10.1016/j.virusres.2026.1997852026-10-31
Elora Kellerstrass, Monika Rinder
Beak and feather disease virus (BFDV, species Circovirus parrot) is the causative agent of psittacine beak and feather disease (PBFD), characterised primary by death of nestlings, feather loss and presumed immunosuppression in parrots worldwide. BFDV shows marked genetic heterogeneity, particularly in the open reading frame 2 (ORF2) encoding the capsid protein (Cap), but the impact of this diversity on antibody recognition has not been systematically assessed. In this study, we used seven recombinant Cap proteins derived from ORF2 variants selected to reflect the diversity of BFDV genotypes circulating in psittacine birds. N-terminally truncated, codon-optimised cap gene constructs were expressed in Escherichia coli and tested by semiquantitative Western blot and indirect ELISA using sera from eight naturally infected, BFDV-PCR-positive psittacine birds. Both assays revealed clear antigen-serum dependent differences in reactivity, with several sera failing to produce detectable signals against some Cap variants under the conditions used. These findings provide experimental evidence that amino acid variation in Cap can be associated with distinct antibody binding patterns in naturally infected birds. The observed heterogeneity in antigen recognition is likely to have direct implications for natural infections with BFDV, for the design and interpretation of BFDV serological assays and should be considered in future development of Cap-based vaccines.
DOI: 10.1016/j.virusres.2026.199791