Epstein-Barr virus reactivation is associated with altered immune cell profiles in peripheral blood and cerebrospinal fluid of treatment-naive multiple sclerosis patients.

Introduction: Acute viral rhinitis is one of the most prevalent upper respiratory conditions, primarily caused by rhinovirus, with other viruses such as coronavirus, adenovirus, RSV, and influenza contributing to smaller proportions. Although diagnosis is typically clinical, laboratory testing plays an increasingly important role in distinguishing between viral and bacterial etiologies, preventing unnecessary antibiotic use, and enhancing clinical decision-making. Methods: A literature search was conducted using PubMed and Google Scholar for articles published from 2020 to 2025. Keywords included “Acute Viral Rhinitis,” “Common Cold,” “Laboratory Diagnosis,” “Multiplex PCR,” and “Point-of-Care Test.” From 89 initially identified studies, screening based on inclusion and exclusion criteria resulted in nine eligible publications. These were synthesized using a narrative review approach and evaluated using the SANRA instrument. Results: Molecular diagnostic methods such as RT-PCR and multiplex PCR demonstrated the highest diagnostic accuracy (>95%) for detecting respiratory viral pathogens. Classic immunological tests, including skin prick testing and ImmunoCAP, remain relevant for assessing allergic rhinitis but are less useful for differentiating between viral and bacterial infections. Basic biomarkers such as CRP and procalcitonin provided moderate sensitivity and supported early clinical screening. Emerging point-of-care tests, particularly assays measuring MxA and CRP, have shown promising accuracy in distinguishing between viral and bacterial infections, making them valuable for primary care settings. Conclusion: No single laboratory method is ideal for diagnosing acute viral rhinitis. A combined approach integrating classical, molecular, and point-of-care diagnostics enhances diagnostic precision and promotes rational antibiotic stewardship. Future practice should prioritize wider access to molecular testing, the adoption of validated point-of-care tools, and the continued development of novel biomarkers to enhance rapid and accurate diagnosis in diverse clinical settings.

Gut-initiated mucosal and systemic immunity against SARS-CoV-2 via an oral hyaluronic acid/chitosan vaccine coacervate.

Adoptive transfer of virus-specific T cells (VSTs) has been used for managing viral diseases in immunocompromised patients, including those undergoing hematopoietic stem cell transplantation and solid organ transplantation. Clinical trials targeting viruses such as cytomegalovirus, Epstein-Barr virus, adenovirus, and BK virus have demonstrated effective viral control without the toxicities associated with conventional antiviral therapies. This review explores the manufacturing, feasibility, safety, and efficacy of VSTs, complemented by 2 case studies illustrating their real-world application. We examine recent advancements in VST manufacturing that broaden their accessibility and applicability to a wider range of viral infections and immunocompromised populations. Key safety considerations, including cytokine release syndrome and graft-versus-host disease, are discussed. Lastly, we assess the expanding applications of VSTs against emerging viral targets, such as COVID-19, and address current barriers to their implementation beyond the research setting.

The transplant environment requires special considerations when testing for viral infections as immunosuppression results in atypical infection profiles. Microbes otherwise considered commensals or causing mild disease can lead to severe infections in transplant environments. Therefore, guidelines tend to recommend broader microbial testing in these populations. In parallel, advances in molecular diagnostics have led to the availability of a wide selection of tests, including highly multiplexed nucleic acid amplification tests (NAATs) and direct next generation sequencing (NGS) based options. These newer technologies may provide information on many potential pathogens simultaneously, more rapidly, and while avoiding invasive specimen collection procedures. However, they are generally more expensive than conventional methods such as culture, and nucleic acid detection of multiple potential pathogens may be nonspecific and confuse the diagnosis. Navigating the complexity of the available molecular test landscape in immunocompromised patients is an opportunity for diagnostic stewardship. Here we discuss the clinical value of different molecular testing strategies for diagnosis of viral infectious diseases in immunocompromised transplant patients using several common transplant infection syndromes as a framework.

Developing a lung-on-a-chip (LOC) platform that is both physiologically and pathologically relevant is crucial due to the mortality and recurrent pandemics of zoonotically transmitted pathogens. This study reports the fabrication of an LOC with an intrinsic air-liquid interface (ALI) via a digital light processing (DLP) 3D bioprinter. The platform architecture supports the localization of different cells, such as human lung epithelial cells (HLEC), human fibroblasts, and human endothelial cells, to mimic their in vivo counterparts. While the air layer of the LOC undergoes cyclic air-breathing via a custom-built lung bioreactor device, the epithelial cells in the LOC express relevant physiological proteins such as aquaporin 5, E-cadherin, and prosurfactant C. Furthermore, the platform incorporates a dynamic perfusion system in the liquid layer of the LOC, which improves the viability of the cells in the inner core of the 3D model and enhances the expression of V-Cadherin and VEGF-A. We mimicked the infection of the airborne SARS-CoV-2 virus to replicate the disease characteristics of the lungs during SARS-CoV-2 infection by the expression of CoV-NP and OAS1 as an innate response to the viral infection. Incorporating the endothelial layer, ALI, 3D hydrogel, air-induced 3D stretching, and airborne viral infection enhances the physiological relevance of the platform, making it an attractive option for respiratory preclinical testing.

Short-chain fatty acids (SCFAs) are gut microbial metabolites produced by gut microbiota from dietary fiber. SCFAs have shown both pro- and anti-viral roles among different viruses and are known to regulate immune functions during infections. However, their role against the Zika virus (ZIKV), in general, and ocular infection, in particular, has never been investigated. In the present study, we aimed to examine the role of three SCFA derivatives: phenylbutyrate (PBA), sodium butyrate (NaB), and sodium acetate (NaAC), on ZIKV replication and associated ocular complications using primary human trabecular meshwork cells (HTMCs) and an IFNAR1-deficient mouse model of ocular infection. Our findings reveal that PBA and NaAc treatment dramatically suppressed the ZIKV replication in HTMCs. NaB showed a slightly less effect than PBA and NaAc. PBA and NaAc treatment significantly attenuated the ZIKV-induced inflammatory cytokine, interferons, and interferon-stimulated genes response via antagonizing the RIG-I/NFκB/MAPKs/STAT1-3 signaling pathways. We discovered that ZIKV induces the expression of free fatty acid receptor 2 (FFAR2)/GPR43 in HTMCs, which is further potentiated by PBA/NaAc. Pharmacological inhibition of FFAR2 abrogated the protective abilities of PBA/NaAc and significantly increased viral replication. Blocking FFAR2 receptors promoted ZIKV-induced cell death, which was suppressed by PBA and NaAc. Butyrate and acetate also inhibited ZIKV binding and cellular entry and inactivated the virus before internalization. PBA and NaAc treatment in mice attenuated the ZIKV-induced ocular manifestations (intraocular pressure, RPE/retinal atrophy, and TM/anterior segment inflammation), which was abrogated by FFAR2 inhibition by 4-CMTB, a selective pharmacological inhibitor of FFAR2. Collectively, our findings indicate that SCFA treatment is an effective approach to limit ZIKV replication and associated ocular damage and may be worth exploring as a means to treat or prevent ZIKV-induced ocular complications/glaucoma in humans.IMPORTANCEZIKV is known to cause severe ocular manifestations in in-utero exposed infants; however, the molecular mechanisms of ZIKV-induced ocular complications remain unknown. SCFAs have demonstrated both pro- and anti-viral roles against different viruses; however, their role against ZIKV is unknown. We showed that SCFAs butyrate and acetate suppress ZIKV transmission and associated ocular complications. The anti-ZIKV activity of these SFACs is mediated via FFAR2, and pharmacological inhibition of FFAR2 promotes ZIKV-induced inflammatory and cell death responses, as well as ocular malformations.

Adoptive immunotherapy with third-party virus-specific T lymphocytes (VSTs) is effective against refractory viral infections. However, its long-term efficacy and persistence must be enhanced. T memory stem cells (TSCMs) with superior self-renewal and multilineage differentiation potential may enhance VSTs durability, although their antiviral capacity is underexplored. Cytomegalovirus (CMV)-and Epstein-Barr virus (EBV)-specific T cells are enriched with CD8⁺ TSCM through cytokine and peptide stimulation. Comprehensive preclinical evaluations show that purified TSCM-VSTs exhibit reduced exhaustion, enhanced expansion, and stronger antiviral activity than central or effector memory VSTs (TCM or TEM). Transcriptomic and epigenetic analyses show significant enrichment of the MAPK and Wnt signaling pathways, consistent with stem-like characteristics. In a murine model, CD8⁺ TSCM VSTs provide more effective protection against Raji-pp65 tumors than TCM or TEM VSTs. In a phase I clinical trial, 10 patients with refractory CMV or EBV infections post-transplant who received third-party, off-the-shelf TSCM-enriched VSTs show a 100% overall response rate and 70% complete response, with persistence up to 12 weeks and no severe adverse events. These findings support TSCM-enriched VSTs as a potent, scalable antiviral immunotherapy and highlight TSCM proportion as a critical determinant of VSTs efficacy.

Thrombocytopenia and absolute neutropenia are recognized manifestations of Epstein-Barr virus infectious mononucleosis (EBV-IM). This study conducted a retrospective analysis of laboratory results from patients clinically suspected of having EBV-IM and tested over a two-year period (2018-2019) at a single testing center in Ireland, aiming to determine the prevalence of these hematological complications. A cohort of 51 confirmed acute EBV-IM cases was established, and the incidence of thrombocytopenia and absolute neutropenia within this group was assessed. These findings were then compared to the frequencies observed in non-acute EBV-IM patients, both with and without atypical lymphocytes. Among the 51 patients diagnosed with acute EBV-IM, 14% presented with thrombocytopenia and absolute neutropenia, including instances of severe cases. A comparable prevalence of these conditions was noted in non-acute EBV-IM patients with identifiable atypical lymphocytes; however, a significantly lower incidence was found in non-acute EBV-IM patients lacking atypical lymphocytes. These results suggest that thrombocytopenia and absolute neutropenia occur in patients with viral infections and are not exclusive to acute EBV-IM.

The onset of COVID-19 and subsequent restrictive measures have impacted various infectious diseases, including hepatitis B virus (HBV). This study explored the epidemiological characteristics of HBV infection in Chinese adults before, during the pandemic, and after the easing of restrictive measures. This population-based cohort study used the data from 23,316 adult patients in the southwest of China who had HBV DNA tests from 1 January 2018 to 31 December 2023. HBV DNA was detected in patient serum using real-time fluorescent quantitative PCR. The positive rate of HBV detection was adjusted by age groups, sex, patient types, and seasons, stratified by the stages of the COVID-19 pandemic. Our analysis revealed significant variations in HBV DNA test positivity rates, primarily influenced by age and the pandemic stages. Positivity rates were highest in the 18-25 age group at 0.50 and decreased with advancing age. Males under 35 were at higher risk. Inpatients had the highest positivity rate at 0.42, with seasonal fluctuations peaking in winter. The pandemic stages significantly affected positivity rates, especially in the 36-45 and 56-65 age groups. The findings highlight a complex interplay between pandemic conditions and observed positivity rates. The increase likely stemmed from multiple factors, including shifted testing focus, altered healthcare-seeking behavior, and potential viral reactivation. The COVID-19 response offers insights for optimizing future viral hepatitis control strategies during public health emergencies. Future research should expand demographic and geographic scope and investigate behavioral/social determinants to elucidate underlying mechanisms and guide targeted interventions.

BackgroundTo assess whether human papillomavirus (HPV) vaccination is associated with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infection among young women in the United States.MethodsWe analyzed data from the 2011-2016 National Health and Nutrition Examination Survey, including sexually active women aged 18-35years with HSV-1 and HSV-2 serology and self-reported HPV vaccination status. Weighted prevalence estimates and logistic regression models were used to evaluate associations, adjusting for demographic and socioeconomic covariates. Propensity score-weighted analyses were conducted as sensitivity checks.ResultsAmong 1643 women, 30.1% reported HPV vaccination. Vaccinated women had lower unadjusted HSV-1 (41.9% vs 47.8%, p = 0.034) and HSV-2 prevalence (9.9% vs 15.2%, p = 0.007). In adjusted models, HPV vaccination was not significantly associated with HSV-1 (aOR = 1.26, 95% CI: 0.94-1.70) or HSV-2 infection (aOR = 0.86, 95% CI: 0.56-1.31). Sensitivity analyses confirmed these findings.ConclusionsHPV vaccination was not linked to increased risk of HSV-1 or HSV-2 infection, providing HSV-specific evidence against sexual risk compensation and supporting public health messaging promoting HPV immunization.

Newcastle Disease (ND) remains a major threat to poultry production worldwide, particularly in regions where it is endemic, like Southern Asia. The disease is caused by virulent forms of avian paramyxovirus-1, commonly termed Newcastle Disease Virus (NDV), a highly contagious virus with significant genetic diversity and evolving pathogenicity. This study aimed to molecularly characterize NDV isolates obtained from chickens and pheasants during the 2020/21 ND outbreaks in Nepal, to understand their genetic makeup, phylogenetic relationships, and implications for control strategies. Necropsy samples, including trachea, liver, intestine, spleen, lungs, heart, and proventriculus were collected from ten birds. Isolates from five clinical samples were typed as NDV by hemagglutination and hemagglutination inhibition (HA/HI) assays and were subjected to whole genome sequencing (WGS). Full genomes of 15,192 nucleotides were recovered from each isolate. Fusion (F) gene sequence analysis revealed the presence of multi-basic cleavage site motif 112RRQKRF117 in all isolates, indicative of virulent strain and suggesting a potentially velogenic or mesogenic phenotype. Phylogenetic analyses consistently classified all isolates within genotype VII.2 of class II NDV. Further comparative analysis indicated a close genetic relationship between the Nepalese isolates and strains reported from India and Bangladesh, and BEAST analysis suggested Southern Asia as the likely source of introduction into Nepal. These viral genomes provide additional insight into contemporary NDV circulating in an area of endemicity.

ABSTRACT Aim To summarise the current paediatric applications of Message RNA (mRNA) vaccines and to identify the key efficacy, safety, and future challenges that must be solved before routine childhood use can be expanded beyond Corona Virus Disease 2019 (COVID‐19). Methods PubMed and ClinicalTrials.gov were searched (up to May 2025) for clinical studies of mRNA vaccines administered to children aged 0–17 years. Search terms combined “mRNA vaccine” with “child”, “infant”, “adolescent”, “paediatric”, “safety”, “immunogenicity”, and “trial”. Results COVID‐19 and RSV mRNA vaccines have effectively reduced the incidence rate among certain age groups of children, while serious adverse events or deaths were rarely observed. Most trials about mRNA vaccines are mainly conducted among adults. More studies are needed to explore the long‐term safety and efficacy of mRNA vaccines in children. Conclusion mRNA vaccines offer rapid, precise, and child‐tailored protection, but robust longitudinal data and public‐science frameworks are urgently needed before their promise can be fully translated into routine paediatric prevention strategies.

The Claims data Learning & Enhancing for Algorithm Refinement (CLEAR) Study: Overview of the Study Design and Baseline Profile.

Antigenic detection is reliably utilized in rapid diagnostic tests and provides a significant time advantage during pandemics and epidemics. Therefore, the rapid detection of viral infections is of great importance and will remain crucial in the future. The SARS-CoV-2 outbreak, which resulted in severe losses, is the most recent example of this necessity. Among rapid diagnostic tests, lateral flow assays (LFAs) are the most practical and do not require specialized equipment, typically being developed using antibody pairs. This study aimed to recombinantly produce a single-chain variable fragment (scFv) specific to the SARS-CoV-2 spike receptor-binding domain (sRBD) and to employ it in the development of lateral flow assays (LFAs) utilizing both antibody and aptamer pairs and an aptamer cocktail. Gold nanoparticles were employed as labeling agents, while both the scFv and full length forms of CR3022, along with aptamers specific to the S and N proteins, were utilized in a sandwich assay format. scFv was produced at a higher concentration and biologically active. It demonstrated effective viral detection in single LFA, Dot Blot Assay (DBA), and multiplex LFA. While single LFA successfully detected only the synthetic target, DBA and multiplex LFA selectively identified the virus in nasopharyngeal and oropharyngeal swab samples. Findings highlight the differences and effectiveness of using scFv in combination with other capture agents and different assay principles for the development of cost-effective and rapid diagnostic tests. scFvs exhibit variable binding in sandwich assays depending on the combinations employed. When used in combination with an aptamer cocktail, scFvs demonstrate enhanced target binding, which is shown for the first time in this study. The use of multiple testing strategies enables a more effective viral diagnosis.

ABSTRACTOncology patients receiving cytostatic therapy used to be at high risk of HBV infection when HBV screening measures were less reliable. Infections acquired under these conditions often persist, like those acquired perinatally or during early infancy. We studied the long‐term clinical outcomes, viral characteristics, and virus‐specific T‐cell immunity of chronic HBV infection acquired during chemotherapy. We examined 16 chronically HBV‐infected former paediatric oncology patients who were infected during cytostatic treatment in the 1980s. Patients underwent physical examination, laboratory liver function testing, non‐invasive measurement of liver stiffness, and determination of HBV serology and DNA levels. If the material was sufficient, HBV sub‐genotype, drug resistance and immune escape mutations, and mutations associated with HBeAg negativity were analysed. The frequency of HBV core‐specific CD8+ T cells was measured after in vitro antigen‐specific expansion. All but one patient were chronically infected with detectable HBsAg but were HBeAg‐negative, mostly with low viraemia. Four patients were under ongoing effective antiviral therapy, and four required treatment initiation due to high viraemia or advanced liver disease. Hepatic effects were predominantly observed in highly viraemic patients. No drug resistance or immune escape mutations were observed. In two highly viraemic patients, basal core promoter and precore region mutations reducing HBeAg expression were identified. HBV core‐specific CD8+ T cells were detected in all patients, but their frequency was low. In conclusion, more than 30 years after primary HBV infection was acquired during chemotherapy, the course of infection still resembles that of perinatally acquired infections.

Oncolytic virus has emerged as a promising candidate against tumors by infecting and killing cancer cells. In addition to poor prognosis of patients with glioma, the exact mechanisms driving the oncolytic virus therapy in glioma remain poorly understood. We employed Enterovirus A71 (EV-A71)-based dataset (GSE136330), vesicular stomatitis virus (VSV)-M51-based dataset (GSE166914) and TCGA-glioma cohort to identify potential candidate gene after oncolytic virus infection. Then we investigated the correlation between glycogenin-2 (GYG2) and crucial outcomes such as clinical features, overall survival, tumor microenvironment. GO enrichment and GSEA analysis were performed to identify GYG2-coexpressed genes and potential regulatory pathways in glioma. The expression level of GYG2 in glioma tissues and cells was evaluated by qRT-PCR. Loss- and gain-of-function and rescue studies were used to explore the functional effect of GYG2 on glioma cell growth and apoptosis in VSV-M51-infected cells. Bioinformatics analysis show that GYG2 is downregulated after VSV-M51 or EV-A71 infection in glioma T98 cells. High expression of GYG2 in glioma is associated with high WHO grade and poor prognosis. In addition, GYG2 expression is linked with immune cell infiltration and immune microenvironment in glioma. GYG2 and its co-expressed protein are involved in regulating integrin 1 pathway and aurora B pathway in glioma. Downregulating GYG2 inhibits glioma cell growth and facilitates tumor cell apoptosis. Importantly, VSV-M51 infection promotes glioma cell apoptosis by downregulating GYG2. Overall, this study advances our knowledge on the mechanisms of oncolytic virus infection and highlights a novel anti-apoptotic effect of GYG2 in glioma, further supporting it as an oncolytic virus target for therapy.

BackgroundOccult hepatitis B virus infection (OBI) carries high risk of transmissibility and pathogenicity. Mutations in the S gene are considered major contributors to OBI development. Our previous study identified the C138R mutation in the S gene of OBI patients. This study aimed to investigate the impact of the C138R mutation on HBsAg function and its mechanisms leading to OBI.MethodsFull-length hepatitis B virus (HBV) plasmids (HBV 1.3, genotype B) and mutant plasmids (HBV C138R) were constructed, along with HA-tagged wild-type (sWT) and mutant (sC138R) S protein expression plasmids. The effects of the C138R mutation on HBsAg antigenicity, secretion, and dimer formation were evaluated through in vitro cell transfection and in vivo hydrodynamic tail vein injection in mice.ResultsThe C138R mutation markedly reduced intra- and extracellular HBsAg levels without affecting HBV transcription, replication, or other viral protein expression. HA-tag assays indicated that this reduction resulted from impaired antigenicity. Several commercial ELISA kits results and HA levels in cell supernatants demonstrated that the C138R mutation also impaired HBsAg secretion. Similarly, the C107R mutation significantly decreased both HBsAg antigenicity and secretion. Non-reducing WB assays and Alphafold 3-based structural predictions revealed that the C138R mutation lead to the formation of aberrant HBsAg dimers. These findings were confirmed in the HBV mouse model.ConclusionThe C138R mutation contributed to OBI by simultaneously impairing HBsAg antigenicity and secretion. Disruption of the disulfide bond between aa107 and aa138, resulting in the formation of structurally abnormal dimers, represented the primary mechanism underlying HBsAg dysfunction caused by this mutation.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-025-07440-z.

B-cell leukemia/lymphoma protein 3 (Bcl3), a member of the IκB family proteins, regulates the transcriptional activities of the NF-κB family of transcription factors. It is known that aberrant Bcl3 activities induce malignancies of both hematologic and non-hematologic origins. Overexpressed, mutated and/or phosphorylated Bcl3 has been implicated in several cancers due to its altered transcriptional activities. However, the physiological function of Bcl3 in immune homeostasis remained elusive to date. In this study, Bcl3 knockout zebrafish were generated to investigate its role in immune regulation. Bcl3 deficient zebrafish exhibited growth retardation and significantly reduced survival. Histological analyses revealed the absence of Hassall bodies in the thymus and hepatocellular nuclear abnormalities, indicating compromised integrity of the immune organs. Zebrafish with Bcl3 deficiency further showed enhanced immune responses and increased susceptibility to both bacterial and viral infections, resulting in significantly elevated levels of pro-inflammatory cytokines il1b, il6, il8, and tnfa. Treatment with the anti-inflammatory drug dexamethasone (Dex) effectively alleviated inflammation, downregulated pro-inflammatory cytokine expressions and improved survival. Collectively, our findings demonstrate Bcl3 as a key regulator of immune activation in vivo, highlighting its role in maintaining immune homeostasis and promoting organismal survival.

Neglected tropical diseases (NTDs) are a diverse group of more than twenty diseases caused by parasitic, bacterial, and viral infections, affecting more than one billion individuals worldwide. Economic evidence can help guide the investment in Community Health Workers (CHWs) who can help expand access to preventive and curative NTD services in low- and middle-income countries (LMICs). A scoping review was conducted across ten databases and grey literature, covering studies published between August 2015 and July 2024. Search terms related to “Community Health Workers” and “Economic Evaluations” were used. Studies were screened via Covidence software based on inclusion and exclusion criteria. Data on study methodology, costs, and outcomes were extracted, tabulated in Microsoft Excel, and analysed. Of the 29 included scenarios (n = 10 studies), 7 were about community mass drug administration and 22 focused on other topics - such as disease-specific prevention and treatment (e.g., dengue). Across scenarios, the most commonly reported outcomes were cost per service delivered (ranging from $0.13-$5.33) and cost per capita (ranging from $10.24-$21.09). Five scenarios reported on cost-effectiveness, with varied results (40–50% of scenarios were reported as cost effective). One study found that interventions were more likely to be cost-effective when they leveraged integrated care as opposed to vertical approaches. The evidence base for economic evaluations regarding CHW involvement in NTD programs is highly limited. From the 10 studies identified there was no clear conclusion with regards to cost-effectiveness or affordability of CHWs in NTD programs in LMICs. To better understand the critical role CHWs can play in both prevention- and treatment-focused NTD programs, further evidence of the cost-effectiveness and affordability of such interventions is needed.