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Keywords = viral pathogens

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11 pages, 782 KB  
Article
First Detection and Genetic Characterization of Influenza D Virus in Cattle in Spain
by Alfredo A. Benito, Luis V. Monteagudo, Sofía Lázaro-Gaspar, Laura Garza-Moreno, Nuria Antón-Baltanás and Joaquín Quílez
Vet. Sci. 2026, 13(2), 130; https://doi.org/10.3390/vetsci13020130 (registering DOI) - 29 Jan 2026
Abstract
Influenza D virus (IDV) and co-circulating respiratory pathogens were investigated using RT-qPCR in 316 samples collected from 210 Spanish cattle farms with bovine respiratory disease (BRD) outbreaks between July 2023 and September 2024. Thirty-eight IDV-positive samples, from 30 farms across 15 provinces throughout [...] Read more.
Influenza D virus (IDV) and co-circulating respiratory pathogens were investigated using RT-qPCR in 316 samples collected from 210 Spanish cattle farms with bovine respiratory disease (BRD) outbreaks between July 2023 and September 2024. Thirty-eight IDV-positive samples, from 30 farms across 15 provinces throughout Spain, were identified. IDV was significantly more frequent in bronchoalveolar lavage samples (22.1%) and nasal swabs (13.5%) compared to lung tissues (5%) and other sample mixtures (5%). All IDV-positive specimens exhibited co-infections, with most (94.7%) harboring three to seven viral and/or bacterial pathogens, highlighting the complexity of BRD outbreaks. Cramer’s V analysis revealed moderate IDV association with Mycoplasma bovis (V = 0.255) and Pasteurella multocida (V = 0.223), and a weaker IDV-bovine coronavirus association (V = 0.202), while IDV association with Histophilus somni (V = 0.025) and bovine herpesvirus 1 (V = 0.000) was negligible. Partial sequences of the hemagglutinin-esterase (HEF) gene from a subset of 13 IDV-positive samples (Ct < 32) were obtained. This confirmed the presence of the two major genetic lineages detected among cattle in Europe, D/OK and D/660, with D/660 exhibiting higher genetic diversity, as determined by DNAsp 6.12 software. This is the first report of IDV infection in Spanish cattle, confirming the circulation of the D/OK and D/660 lineages within the cattle population. Full article
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35 pages, 5035 KB  
Review
Progress in the Expression, Purification, and Characterization of Recombinant Collagen
by Youlin Deng, Jiyao Kang, Xiaoqun Duan, Yingjun Kong, Weiquan Xie, Dongjie Lei, Tingchun Wang and Guifeng Zhang
Bioengineering 2026, 13(2), 159; https://doi.org/10.3390/bioengineering13020159 - 28 Jan 2026
Abstract
Synthesized by expressing natural collagen sequences in specific hosts, recombinant collagen exhibits multiple advantages, encompassing a higher content of bioactive domains, enhanced antioxidant activity, the absence of viral pathogens, favorable hydrophilicity, reproducible production, and low immunogenicity. Consequently, it has found extensive use in [...] Read more.
Synthesized by expressing natural collagen sequences in specific hosts, recombinant collagen exhibits multiple advantages, encompassing a higher content of bioactive domains, enhanced antioxidant activity, the absence of viral pathogens, favorable hydrophilicity, reproducible production, and low immunogenicity. Consequently, it has found extensive use in applications ranging from biomaterials and pharmaceuticals to skincare. This review systematically explores various expression systems for recombinant collagen, including those utilizing Escherichia coli, Pichia pastoris, plants, insect baculovirus, and mammalian cells. It provides a detailed comparison of their differences and commonalities in terms of production efficiency, post-translational modification capability, and cost-effectiveness. Key separation and purification techniques for recombinant collage-notably precipitation, affinity chromatography, ion-exchange chromatography, and gel filtration chromatography are further introduced, with an in-depth analysis of the applicable scenarios and purification outcomes for each method. Finally, the review comprehensively summarizes the characterization methods for both the physicochemical properties and biological functions of recombinant collagen. For physicochemical properties, techniques covered include scanning electron microscopy, micro-differential thermal analysis, circular dichroism spectroscopy, SDS-PAGE, mass spectrometry, and Fourier-transform infrared spectroscopy. For biological functions, the focus is on its roles and the corresponding assessment methods in processes such as cell proliferation, migration, adhesion, and wound healing. Building upon this comprehensive overview, current challenges facing recombinant collagen are identified, and future directions are proposed, emphasizing the need to reduce R&D costs, refine testing methods for cosmetic products, and improve safety evaluation protocols to advance the field. Full article
(This article belongs to the Topic Advances in Biomaterials—2nd Edition)
13 pages, 1908 KB  
Communication
Antigenic Matching of rHVT-H5 via CRISPR/Cas9 Confers Complete Protection Against Novel H5N1 Clade 2.3.4.4b in Chicken
by Sang-Won Kim, Jong-Yeol Park, Ji-Eun Son, Cheng-Dong Yu, Ki-Woong Kim, Won-Bin Jeon, Yu-Ri Choi, Hyung-Kwan Jang, Bai Wei and Min Kang
Vet. Sci. 2026, 13(2), 127; https://doi.org/10.3390/vetsci13020127 - 28 Jan 2026
Abstract
The widespread panzootic of clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 necessitates the development of vaccine platforms capable of rapid adaptation to emerging antigenic variants. Although commercial recombinant turkey herpesvirus (rHVT) vaccines are available, they often utilize heterologous inserts that may fail [...] Read more.
The widespread panzootic of clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 necessitates the development of vaccine platforms capable of rapid adaptation to emerging antigenic variants. Although commercial recombinant turkey herpesvirus (rHVT) vaccines are available, they often utilize heterologous inserts that may fail to optimally limit viral shedding of novel field strains. Here, we report the rapid construction of a homologous rHVT-H5 vaccine expressing the hemagglutinin (HA) gene of a representative clade 2.3.4.4b isolate via CRISPR/Cas9-mediated non-homologous end joining (NHEJ). In vitro characterization confirmed stable HA surface expression and growth kinetics comparable to the parental virus. In specific-pathogen-free (SPF) chickens, rHVT-H5 elicited robust hemagglutination inhibition (HI) antibody titers. Following lethal challenge with a homologous clade 2.3.4.4b H5N1 virus, the vaccine conferred 100% protection against mortality and clinical signs while significantly reduced oropharyngeal sheddings and completely inhibited viral shedding in cloacal samples. These findings demonstrate that an antigenically matched rHVT-H5 constitutes a promising strategy for mitigating the ongoing global threat posed by clade 2.3.4.4b HPAI H5N1. Full article
(This article belongs to the Special Issue Exploring Innovative Approaches in Veterinary Health)
22 pages, 1738 KB  
Article
Tissue-Specific Multi-Omics Integration Demonstrates Molecular Signatures Connecting Obesity to Immune Vulnerability
by Ozge Onluturk Aydogan, Aytac Dursun Oksuzoglu and Beste Turanli
Metabolites 2026, 16(2), 95; https://doi.org/10.3390/metabo16020095 - 27 Jan 2026
Abstract
Background: Adipose tissue surrounds organs and tissues in the body and can alter their function. It could secrete diverse biological molecules, including lipids, cytokines, hormones, and metabolites. In light of all this information, obesity can influence many tissues and organs in the body, [...] Read more.
Background: Adipose tissue surrounds organs and tissues in the body and can alter their function. It could secrete diverse biological molecules, including lipids, cytokines, hormones, and metabolites. In light of all this information, obesity can influence many tissues and organs in the body, and this situation makes obesity a central contributor to multiple disorders. It is very important to investigate the crosstalk between tissues and organs in the body to clarify the key mechanisms of obesity. Methods: In this study, we analyzed the gene expression profiles of the liver, skeletal muscle, blood, visceral, and subcutaneous adipose tissue. Differentially expressed genes (DEGs) were identified for each tissue, and functional enrichment and protein–protein interaction network analyses were performed on genes commonly identified across tissues. Priority candidate genes were identified using network-based centrality measures, and potential molecular intersection points were explored through host-pathogen interaction network analysis. This study provides an integrative framework for characterizing inter-tissue molecular patterns associated with obesity at the network level. Results: The muscle, subcutaneous adipose tissue, and blood have the highest number of DEGs. The subcutaneous adipose tissue and blood stand out due to the number of DEGs they possess, although liver and visceral adipose tissue have lower amounts. Cancer ranks first in terms of diseases associated with obesity, and this association is accompanied by leukemia, lymphoma, and gastric cancer. RPL15 and RBM39 are the top genes in both degree and betweenness metrics. The host–pathogen interaction network consists of 13 unique-host proteins, 54 unique-pathogen proteins, and 27 unique-pathogen organisms, and the Influenza A virus had the highest interaction. There were a small number of common metabolites in all tissues: 2-Oxoglutarate, Adenosine, Succinate, and D-mannose. Conclusions: In this study, we aimed to identify candidate molecules for obesity using an integrative approach, examining the gene profiles of different organs and tissues. The findings of this study suggest a possible link between obesity and immune-related biological processes. The network obtained from the host-pathogen interaction analysis, and especially the pathways associated with viral infections that stand out in the functional enrichment analysis, may overlap with molecular signatures linked to obesity. Furthermore, the co-occurrence of cytokine signaling, insulin, and glucose metabolism pathways in the enrichment results indicates that the response of cells to insulin may be affected in obese individuals, suggesting a potential interaction between immune and metabolic processes; however, further experimental validation is needed to reveal the direct functional effects of these relationships. Full article
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11 pages, 580 KB  
Article
Molecular Epidemiology and Genotype Diversity of Severe Fever with Thrombocytopenia Syndrome Virus in Goats in South Korea
by In-Ohk Ouh
Int. J. Mol. Sci. 2026, 27(3), 1264; https://doi.org/10.3390/ijms27031264 - 27 Jan 2026
Abstract
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne zoonotic pathogen of significant public health concern in South Korea, where human cases continue to occur at high levels; however, information on the molecular epidemiology and genotype diversity of SFTSV in goats—an increasingly [...] Read more.
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne zoonotic pathogen of significant public health concern in South Korea, where human cases continue to occur at high levels; however, information on the molecular epidemiology and genotype diversity of SFTSV in goats—an increasingly important livestock species—remains limited. In this study, blood samples were collected from 750 clinically healthy goats during nationwide surveillance in 2024. Viral RNA was detected by RT-PCR targeting the S and M genomic segments. Epidemiological characteristics were analyzed according to season, region, farm size, breed, and sex. Positive samples were subjected to sequencing and phylogenetic analysis to determine SFTSV genotypes. SFTSV RNA was detected in 10 of 750 goats (1.3%), with significantly higher detection rates in autumn compared with summer, in southern regions compared with northern regions, and in female goats compared with males, while no significant association was observed with farm size or breed. Phylogenetic analysis showed that goat-derived SFTSV strains belonged to genotypes B2, D, and F; notably, genotypes D and F were identified in goats for the first time in South Korea. These findings indicate that goats are exposed to genetically diverse SFTSV strains circulating in tick populations and exhibit epidemiological patterns consistent with tick ecology and human SFTS incidence, supporting the role of goats as incidental or sentinel hosts. Continuous molecular surveillance of goats, integrated with vector monitoring programs, may enhance understanding of regional SFTSV transmission dynamics and facilitate early detection of emerging genotypes with public health implication. Full article
(This article belongs to the Special Issue Molecular and Genomic Basis of Viral Variation and Host Adaptation)
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23 pages, 20739 KB  
Article
Cross-Species Analysis of Transcriptomic Response to Alpha-Herpesvirus Infection in Human, Bovine and Equine Cells
by Mirko Schmitz, Eva Neugebauer, Florian Full and Kristen L. Conn
Int. J. Mol. Sci. 2026, 27(3), 1261; https://doi.org/10.3390/ijms27031261 - 27 Jan 2026
Abstract
Comparative transcriptomics offers a powerful approach to elucidate host–virus interactions across related pathogens, yet systematic evaluations across species-matched cellular systems remain limited. We performed a cross-species RNA sequencing analysis of respective species’ cells infected with three alphaherpesviruses—herpes simplex virus 1 (HSV-1), bovine alphaherpesvirus [...] Read more.
Comparative transcriptomics offers a powerful approach to elucidate host–virus interactions across related pathogens, yet systematic evaluations across species-matched cellular systems remain limited. We performed a cross-species RNA sequencing analysis of respective species’ cells infected with three alphaherpesviruses—herpes simplex virus 1 (HSV-1), bovine alphaherpesvirus 1 (BHV-1), and equid alphaherpesvirus 1 (EHV-1)—to dissect conserved and virus-specific transcriptional responses. We show that certain orthologous genes and orthologous pathways are differentially regulated upon infection among the three species like pathways related to translation rRNA processing and TNF-alpha signalling. We find that the earliest sampled timepoint of infection, 2 h post infection (hpi), shows the most commonly enriched pathways among the three species compared to later timepoints. At 6 h and 9 h post infection, BHV-1- and EHV-1 infections have more in common with each other in terms of enriched pathways than with HSV-1 infections. Moreover, we provide a comprehensive analysis of temporal viral gene expression for all three herpesviruses. Together, these findings provide a comparative framework for understanding alphaherpevirus–host interactions and reveal both conserved core responses and species-specific transcriptional signatures. This work establishes a foundation for identifying broadly acting antiviral targets as well as virus-specific vulnerabilities that may inform host-directed therapies and cross-species disease management. Full article
(This article belongs to the Special Issue The Interaction Between Cell and Virus, 3rd Edition)
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17 pages, 1234 KB  
Article
Long-Term Protective Immune Responses Induced by rBCG-RBD/rRBD Heterologous Prime/Boost Immunization Strategy: Fusion of RBD-Wuhan with LTB Adjuvant Induces Cross-Reactivity with SARS-CoV-2 Variant Omicron
by Giana Carla Gaboardi, Monalisa Martins Trentini, Alex Issamu Kanno, Luana Moraes, Arthur Daniel Januzzi, Lennon Ramos Pereira, Greicy Brisa Malaquias Dias, Luciano Fernandes Huergo, Sergio C. Oliveira, André Bafica and Luciana Cezar de Cerqueira Leite
Vaccines 2026, 14(2), 120; https://doi.org/10.3390/vaccines14020120 - 27 Jan 2026
Abstract
Background/Objectives: SARS-CoV-2, the causative agent of COVID-19, has been responsible for more than seven million deaths worldwide since its emergence. The Bacillus Calmette–Guérin (BCG) vaccine, used for over 100 years to prevent tuberculosis, induces a Th1-prominent immune response that is important for [...] Read more.
Background/Objectives: SARS-CoV-2, the causative agent of COVID-19, has been responsible for more than seven million deaths worldwide since its emergence. The Bacillus Calmette–Guérin (BCG) vaccine, used for over 100 years to prevent tuberculosis, induces a Th1-prominent immune response that is important for protection against Mycobacterium tuberculosis, other mycobacteria, and intracellular pathogens. BCG has also been shown to induce innate immune memory and heterologous protection against non-related infections. Additionally, BCG has been used as a vector to express heterologous proteins, showing protective effects against various diseases, particularly respiratory viral infections, including SARS-CoV-2. In this report, we constructed two recombinant BCG strains as potential vaccine candidates based on the receptor-binding domain (RBD) of the Spike antigen: one expressing only the RBD protein (rBCG-RBD) and another expressing the RBD protein in fusion with the LTB (Escherichia coli Labile Toxin subunit B) adjuvant (rBCG-LTB-RBD). Methods: We evaluated the induction of SARS-CoV-2-specific humoral and cellular immune responses using these vaccine candidates in a prime–boost strategy with a booster dose using the rRBD protein (produced in cell culture) and the Alum adjuvant. Antisera were evaluated for neutralization of the Wuhan and Omicron SARS-CoV-2 pseudotyped virus. Results: Either immunization scheme (rBCG-RBD/rRBD or rBCG-LTB-RBD/rRBD) induced high IgG antibody titers, with antibody neutralization against a Wuhan SARS-CoV-2 pseudotyped virus after 10 weeks. The antibody levels induced by rBCG-RBD/rRBD were maintained for up to 9 months. Interestingly, only the sera from mice receiving the prime–boost with rBCG-LTB-RBD/rRBD showed cross-reactive neutralization against the Omicron SARS-CoV-2 pseudotyped virus. Immunization with rBCG-RBD or rBCG-LTB-RBD and a rRBD booster dose promoted the induction of specific CD4+ and CD8+ T cells producing Th1/Th2 cytokines (IL-4, TNF-α and IFN-γ). Conclusions: Our study highlights the potential of the prime–boost immunization strategy using rBCG-RBD/rRBD to induce long-term immunity and rBCG-LTB-RBD/rRBD to induce cross-protection against different variants, both of which could serve as promising vaccine candidates. Full article
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2 pages, 129 KB  
Editorial
Special Issue on Efficacy, Safety, and Immunogenicity of Vaccines Against Viruses: From Network Medicine to Clinical Experimentation
by Pietro Hiram Guzzi, Jayanta Kumar Das and Marianna Milano
Viruses 2026, 18(2), 165; https://doi.org/10.3390/v18020165 - 27 Jan 2026
Abstract
In an era defined by the constant emergence of novel viral threats—from rapidly evolving SARS-CoV-2 variants to endemic pathogens such as influenza and orthohantaviruses—the scientific community is continually challenged to refine the tools and strategies that shape modern vaccinology [...] Full article
29 pages, 3654 KB  
Article
Direct Cytoplasmic Transcription and Trimeric RBD Design Synergize to Enhance DNA Vaccine Potency Against SARS-CoV-2
by Yunju Nam, Sang Chul Shin, Sang Won Cho and Hyung Jun Ahn
Pharmaceutics 2026, 18(2), 164; https://doi.org/10.3390/pharmaceutics18020164 - 26 Jan 2026
Abstract
Background/Objectives: The emergence of immune-evasive SARS-CoV-2 variants highlights the need for adaptable vaccine strategies. Trimeric receptor-binding domain (tRBD) antigens offer structural and immunological advantages over monomeric RBDs, but DNA vaccine efficacy has been limited by inefficient antigen expression, particularly in non-dividing antigen-presenting cells. [...] Read more.
Background/Objectives: The emergence of immune-evasive SARS-CoV-2 variants highlights the need for adaptable vaccine strategies. Trimeric receptor-binding domain (tRBD) antigens offer structural and immunological advantages over monomeric RBDs, but DNA vaccine efficacy has been limited by inefficient antigen expression, particularly in non-dividing antigen-presenting cells. Although cytoplasmic transcription–based DNA platforms have been developed to overcome nuclear entry barriers, their utility for antigen structure–function optimization remains underexplored. This study evaluated whether integrating a rationally designed trimeric RBD with a T7-driven cytoplasmic transcription system could enhance immunogenic performance. Methods: A DNA vaccine encoding a tandem trimeric SARS-CoV-2 RBD was delivered using a T7 RNA polymerase-driven cytoplasmic transcription system. In vitro antigen expression was assessed following Lipofectamine 3000-mediated transfection. In vivo, mice were immunized with the SM-102-based Rpol/tRBD/LNP formulation, and immunogenicity was assessed by antigen-specific antibody titers, serum neutralizing activity, and T-cell response profiling, together with basic safety/tolerability evaluations. Results: The T7-driven cytoplasmic transcription system markedly increased antigen mRNA and protein expression compared with conventional plasmid delivery. Rpol/tRBD vaccination induced higher anti-RBD IgG titers, enhanced neutralizing antibody activity, and robust CD8⁺ T cell responses relative to monomeric RBD and plasmid-based trimeric RBD vaccines. Immune responses were Th1-skewed and accompanied by germinal center activation without excessive inflammatory cytokine induction, body-weight loss, or hepatic and renal toxicity. Conclusions: This study demonstrates that integrating rational trimeric antigen engineering with direct cytoplasmic transcription enables balanced and well-tolerated immune activation in a DNA vaccine context. The T7 autogene-based platform provides a flexible framework for antigen structure–function optimization and supports the development of next-generation DNA vaccines targeting rapidly evolving viral pathogens. Full article
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53 pages, 1872 KB  
Review
Hepatoprotective Potential of Curcumin in the Prevention of Liver Dysfunction in a Porcine Model
by Kamila Kibitlewska, Varunkumar Asediya, Krzysztof Karpiesiuk, Urszula Czarnik, Marek Lecewicz, Paweł Wysocki, Prarthana Sharma, Iwona Otrocka-Domagała, Łukasz Zielonka, Andrzej Pomianowski, Adam Okorski, Garima Kalra, Sharmin Sultana, Nihal Purohit, Adam Lepczyński, Małgorzata Ożgo, Marta Marynowska, Agnieszka Herosimczyk, Elżbieta Redlarska, Brygida Ślaska, Krzysztof Kowal, Angelika Tkaczyk-Wlizło, Paweł Grychnik, Athul P. Kurian, Kaja Ziółkowska-Twarowska, Grzegorz Roman Juszczak, Mariusz Pierzchała, Katarzyna Chałaśkiewicz, Katarzyna Kępka-Borkowska, Ewa Poławska, Rafał Radosław Starzyński, Magdalena Ogłuszka, Hiroaki Taniguchi, Frieder Hadlich, Henry Reyer, Michael Oster, Nares Trakooljul, Avon Augustin Nalpadan, Siriluck Ponsuksili, Klaus Wimmers, Chandra Shekhar Pareek and Wojciech Kozeraadd Show full author list remove Hide full author list
Nutrients 2026, 18(3), 408; https://doi.org/10.3390/nu18030408 - 26 Jan 2026
Abstract
Curcumin, the major polyphenolic constituent of Curcuma longa, has been widely investigated as a hepatoprotective adjunct due to its antioxidant and immunomodulatory properties. This review evaluates the relevance of curcumin for the prevention and management of liver dysfunction and hepatitis in pigs [...] Read more.
Curcumin, the major polyphenolic constituent of Curcuma longa, has been widely investigated as a hepatoprotective adjunct due to its antioxidant and immunomodulatory properties. This review evaluates the relevance of curcumin for the prevention and management of liver dysfunction and hepatitis in pigs by synthesizing available porcine evidence and integrating mechanistic insights from translational liver injury models where pig-specific data remain limited. Across experimental hepatic injury contexts, curcumin administration is most consistently associated with reduced biochemical and structural indicators of hepatocellular damage, including decreased aminotransferase activity, attenuation of lipid peroxidation, and enhancement of endogenous antioxidant defenses. These effects are mechanistically linked to suppression of pro-inflammatory signaling pathways, particularly NF-κB-related transcriptional activity and inflammasome-associated responses, together with reduced expression of key cytokines such as TNF-α, IL-1β, and IL-6. Concurrent activation of Nrf2-centered cytoprotective pathways and induction of phase II antioxidant enzymes (including HO-1, GST, and NQO1) appear to constitute a conserved axis supporting hepatic oxidative stress resilience. In swine-relevant infectious settings, available data further support antiviral activity against selected porcine pathogens, including classical swine fever virus and porcine reproductive and respiratory syndrome virus, potentially mediated through interference with lipid-dependent stages of viral replication and modulation of Kupffer cell activation. Although combination strategies with established hepatoprotective approaches are conceptually attractive, current synergy evidence remains heterogeneous and largely extrapolated. Overall, curcumin represents a plausible adjunct candidate for supporting porcine liver health; however, translation into practice will depend on resolving formulation-dependent bioavailability constraints and strengthening the pig-specific evidence base. Full article
(This article belongs to the Section Lipids)
21 pages, 862 KB  
Review
Targeting the MR1-MAIT Cell Axis for Vaccination Against Infectious Disease
by Mattie S. M. Timmer, Lisa M. Connor and Bridget L. Stocker
Vaccines 2026, 14(2), 117; https://doi.org/10.3390/vaccines14020117 - 26 Jan 2026
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Abstract
Mucosal-associated invariant T (MAIT) cells exist in high numbers in the body and have a unique and highly conserved T cell receptor (TCR). They can be activated in a TCR-dependent manner by ligands presented on the monomorphic protein MHC class I-related protein 1 [...] Read more.
Mucosal-associated invariant T (MAIT) cells exist in high numbers in the body and have a unique and highly conserved T cell receptor (TCR). They can be activated in a TCR-dependent manner by ligands presented on the monomorphic protein MHC class I-related protein 1 (MR1) which is found on many cell types, including professional antigen presenting cells (APCs) and epithelial cells. This has sparked interest in the potential to exploit the MR1-MAIT cell axis for the development of vaccines against infectious disease. Within this context an MR1 ligand, typically 5-(2-oxopropylideneamino)-d-ribitylaminouracil (5-OP-RU), is administered with or without a Toll-like receptor (TLR) ligand or cytokine in a pan vaccination approach that would prime the immune response to provide protection against a variety of bacterial and viral pathogens. This strategy has led to enhanced protection in murine models of Legionella longbeachae, Francisella tularensis, Klebsiella pneumoniae, Streptococcus pneumoniae and influenza infection. However, studies against Mycobacterium tuberculosis infection have proven less successful. The second vaccination approach involves pairing the MR1 ligand with more conventional antigens that could activate CD4+ and/or CD8+ T cells. This approach has been successful in murine models of cholera, influenza, and SARS-CoV-2, including in the context of subunit vaccines. However, there are several challenges when using MR1-MAIT cell-mediated vaccine adjuvants. These include the inherent instability of 5-OP-RU and the need for more advanced studies to better understand how the use of MR1 ligands would translate to applications in humans. This review will discuss these aspects and highlight the mechanistic studies that have been undertaken to understand how MAIT cells might elicit their effects within the context of MAIT cell-mediated vaccines for infectious disease. Full article
(This article belongs to the Special Issue Next-Generation Platforms for Vaccine Design and Immune Evaluation)
20 pages, 931 KB  
Review
Cellular and Molecular Mechanisms of SARS-CoV-2 Spike Protein-Induced Endothelial Dysfunction
by Kelsey C. Muir, Dwight D. Harris, Meghamsh Kanuparthy, Jiayu Hu, Ju-Woo Nho, Christopher Stone, Debolina Banerjee, Frank W. Sellke and Jun Feng
Cells 2026, 15(3), 234; https://doi.org/10.3390/cells15030234 - 26 Jan 2026
Viewed by 42
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the viral spike proteins, which are key structural components that mediate host cell binding and entry and alter downstream signaling through multiple interactions with endothelial surface receptors. Endothelial dysfunction is a central [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is initiated by the viral spike proteins, which are key structural components that mediate host cell binding and entry and alter downstream signaling through multiple interactions with endothelial surface receptors. Endothelial dysfunction is a central consequence of COVID-19, contributing to vascular inflammation, barrier disruption, thrombosis, and multi-organ injury affecting the pulmonary, cardiovascular, cerebral, and renal systems. Emerging evidence demonstrates that spike protein-mediated effects, independent of productive viral infection, disrupt endothelial homeostasis through angiotensin-converting enzyme 2 (ACE2) dysregulation, integrin engagement, altered calcium signaling, junctional protein remodeling, oxidative stress, and pro-inflammatory and pro-apoptotic pathways. This review is intentionally focused on spike (S) protein-driven mechanisms of endothelial dysfunction; pathogenic vascular effects attributed to other SARS-CoV-2 structural proteins, including the nucleocapsid (N) protein, are beyond the scope of this discussion. In this review, we synthesize current experimental and translational data detailing the molecular mechanisms by which the SARS-CoV-2 spike protein drives endothelial dysfunction across multiple organ systems and discuss potential therapeutic strategies aimed at preserving endothelial integrity in acute COVID-19 and its long-term vascular sequela. Full article
(This article belongs to the Special Issue Endothelial Dysfunction in Vascular Diseases)
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13 pages, 294 KB  
Systematic Review
The Impact of Disinfecting Non-Sterile Disposable Gloves on the Level of Microbiological Contamination in Clinical Practice
by Anna Gajkiewicz, Julia Szymczyk, Sandra Lange and Wioletta Mędrzycka-Dąbrowska
Microorganisms 2026, 14(2), 286; https://doi.org/10.3390/microorganisms14020286 - 26 Jan 2026
Viewed by 48
Abstract
Gloves, used in conjunction with hand hygiene, are designed to protect healthcare personnel from direct contact with blood, body fluids, and other potentially infectious materials, which is critical for reducing the transmission of microorganisms. The aim of this systematic review was to analyze [...] Read more.
Gloves, used in conjunction with hand hygiene, are designed to protect healthcare personnel from direct contact with blood, body fluids, and other potentially infectious materials, which is critical for reducing the transmission of microorganisms. The aim of this systematic review was to analyze available studies on the disinfection of disposable, non-sterile gloves as a method of reducing the risk of microbial contamination in everyday clinical practice. A systematic review was conducted in the fourth quarter of 2025. A total of 317 records were initially retrieved from the five databases (EBSCO, PubMed, Scopus, Web of Science, Ovid). Interventions included alcohol-based hand rubs (ABHR), sodium hypochlorite wipes or solutions, quaternary ammonium wipes, and sporicidal ethanol. Across all studies, glove disinfection consistently reduced bacterial, viral, and spore contamination. Hypochlorite-based agents and sporicidal ethanol demonstrated the highest efficacy against spore-forming organisms such as Clostridioides difficile. Alcohol-based hand rubs were effective against bacteria and enveloped viruses but showed reduced activity against non-enveloped viruses and spores. Conclusions from studies conducted in both laboratory and clinical conditions clearly emphasize the key role of hand hygiene after removing gloves, even when using multiple layers of protection, while also indicating that glove disinfection can be a useful supplement to protection against particularly virulent pathogens (EVD, CDI). Full article
(This article belongs to the Section Public Health Microbiology)
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19 pages, 1058 KB  
Review
Beyond Viral Restriction: The Metabolic Dimensions of Interferon-Stimulated Genes in Antiviral Immunity
by Xiaoyu Ding, Libao Liu and Haiming Wei
Viruses 2026, 18(2), 160; https://doi.org/10.3390/v18020160 - 25 Jan 2026
Viewed by 87
Abstract
Interferon-stimulated genes (ISGs) are classically recognized for their direct antiviral functions, such as viral genome degradation or replication blockade. However, emerging evidence reveals that ISGs orchestrate a broader landscape of host defense by rewiring cellular metabolism. These mechanisms are still not fully understood [...] Read more.
Interferon-stimulated genes (ISGs) are classically recognized for their direct antiviral functions, such as viral genome degradation or replication blockade. However, emerging evidence reveals that ISGs orchestrate a broader landscape of host defense by rewiring cellular metabolism. These mechanisms are still not fully understood in the context of antiviral immunity. This review synthesizes recent advances in understanding how ISGs modulate metabolic pathways (e.g., glycolysis, lipid metabolism, amino acids, and nucleotide metabolism) to create an antiviral cellular environment. However, viruses have developed strategies to evade or counteract ISG-encoded proteins, and some even hijack certain ISGs to their advantage. Therefore, we further explore how viruses subvert these ISG-driven metabolic to evade host defenses. Overall, we summarize the current state of knowledge on the interactions between viruses and ISGs and propose that ISGs act as “protective” or “pathogenic” regulators at the dimensions of metabolism, offering new perspectives for targeting host-centered pathways to combat viral infections. Full article
(This article belongs to the Special Issue Interferon-Stimulated Genes in Antiviral Immunity)
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27 pages, 14815 KB  
Article
The Safety of Alcaligenes Lipid A in a Virus-Induced Immune Disease Model Associated with IgA, Th17 Cells, and Microbiota
by Ijaz Ahmad, Seiichi Omura, Sundar Khadka, Fumitaka Sato, Ah-Mee Park, Cong Thanh Nguyen, Sandesh Rimal, Koichi Fukase, Atsushi Shimoyama and Ikuo Tsunoda
Viruses 2026, 18(2), 155; https://doi.org/10.3390/v18020155 (registering DOI) - 23 Jan 2026
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Abstract
Lipid A is a component of lipopolysaccharide (LPS) of Gram-negative bacteria. Previously, we demonstrated that synthesized lipid A derived from Alcaligenes faecalis (ALA) could enhance antigen-specific immunoglobulin (Ig) A and T helper (Th) 17 responses, when ALA was co-administered experimentally with an antigen [...] Read more.
Lipid A is a component of lipopolysaccharide (LPS) of Gram-negative bacteria. Previously, we demonstrated that synthesized lipid A derived from Alcaligenes faecalis (ALA) could enhance antigen-specific immunoglobulin (Ig) A and T helper (Th) 17 responses, when ALA was co-administered experimentally with an antigen as a vaccine adjuvant. This raised concerns about the safety of the ALA usage, since IgA and Th17 responses have been suggested to play a pathogenic role in several immune-mediated diseases, including multiple sclerosis (MS). We investigated whether ALA administrations could exacerbate an animal model of MS, Theiler’s murine encephalomyelitis virus (TMEV) infection. TMEV-infected SJL/J mice were administered ALA at various time points, and their neurological signs were observed for 7 weeks. We found that ALA administrations did not exacerbate TMEV-induced inflammatory disease or viral persistence in the central nervous system (CNS), clinically or histologically. Furthermore, ALA administrations did not enhance TMEV-specific humoral and cellular responses, including IgA and Th17 responses. On the other hand, principal component analysis (PCA) of the fecal, not the ileal, samples showed significant changes in the microbiota, characterized by increases in the relative abundance of bacteria belonging to the phylum Bacteroidota, including the genera Alistipes and Bacteroides. Therefore, ALA injections could be safe for use in immune-mediated diseases, whose immunopathology has been associated with IgA and Th17 responses. Full article
(This article belongs to the Section General Virology)
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