PUBLICATIONS

SARS-CoV-2 infection is linked to hematologic abnormalities, but whether early hematopoietic compartments and their stromal niche are directly engaged remains unclear. We used in vitro exposure models to compare variant-associated responses of adult mesenchymal stromal cells (MSCs) and umbilical cord blood (UCB) CD34 ⁺ hematopoietic stem and progenitor cells (HSPCs). Adipose-derived (AD) and bone marrow-derived (BM) MSCs exposed to wild-type, Delta, or Omicron showed source- and variant-dependent nucleocapsid protein (NP) positivity, highest with Omicron in AD-MSCs; infectious virus in supernatants was undetectable. AD-MSCs expressed higher neuropilin-1 (NRP1) than BM-MSCs, and NRP1 knockdown reduced Omicron-associated NP signal, implicating an NRP1-linked entry process. SARS-CoV-2 exposure induced indoleamine-2,3-dioxygenase 1 (IDO1), most prominently in AD-MSCs. In UCB CD34 ⁺ HSPCs, Omicron increased NP positivity enriched in long-term HSCs, reduced primitive fraction frequencies, increased colony formation, and promoted early erythroid progenitor accumulation; heat-inactivated virus did not. NanoString profiling revealed host-response activation and altered cell-cycle/differentiation programs. These data indicate Omicron can engage stromal and early hematopoietic compartments and remodel stress-responsive hematopoiesis.

Respiratory viral infections continue to pose a significant global health burden, highlighting the urgent need for broad-spectrum antiviral therapeutics. In this study, we identified ECDD-S16, an arylnaphthalene lignan derivative, as a potent broad-spectrum antiviral. ECDD-S16 exhibited dose-dependent antiviral activity against influenza A (H1N1 and H3N2), influenza B, SARS-CoV-2, and respiratory syncytial virus (RSV) in mammalian cell cultures, with selectivity indices (SI) up to 3,194 against H1N1, representing a marked improvement over the parent arylnaphthalene lignans. Using influenza A (H1N1) as a mechanistic model, we show that ECDD-S16 acts during the early stage of the viral life cycle. Time-of-addition analysis localized its activity predominantly to the first hour of infection, while LysoTracker staining demonstrated that ECDD-S16 markedly reduced the accumulation of acidic vesicles. Co-localization analyses with the early and late endosomal markers EEA1 and LAMP1 further revealed altered association of viral antigen with endosomal compartments. Nevertheless, bypassing endosomal acidification by triggering fusion at the plasma membrane restored infection only partially, and ECDD-S16 also inhibited HA-mediated fusion when the acidic trigger was supplied externally. Collectively, these findings identify ECDD-S16 as a promising broad-spectrum antiviral candidate that interferes with an early, pH-dependent step of influenza virus entry. These results establish ECDD-S16 as a promising broad-spectrum antiviral candidate for further development against respiratory viral infections.

Influenza A viruses (IAVs), particularly highly pathogenic avian influenza (HPAI) strains like H5N1 and H7N9, cause severe pneumonia and acute respiratory distress syndrome (ARDS) driven by dysregulated cytokine storms. A key mediator of this immunopathology is the excessive activation of the NLRP3 inflammasome, which governs the maturation of IL-1β. Galectin-3 (Gal3), a β-galactoside-binding lectin, is upregulated during infection; however, its specific regulatory role in coordinating NLRP3 inflammasome activation across distinct viral hemagglutinin (HA) subtypes remains to be elucidated. In this study, we demonstrate that Gal3 functions as a critical amplifier of influenza pathogenesis through a distinct dual-stage mechanism. Results from viral binding and internalization assays indicate that extracellular Gal3 promotes viral entry by interacting with viral HA, an effect that is strictly strain-dependent (H5N1 > H1N1 > H7N9). This enhanced entry consequently amplifies the initial signal for inflammasome activation. Intracellularly, Gal3 regulates the NLRP3 cascade by sustaining NF-κB activation (priming) to upregulate NLRP3 and pro-IL-1β transcription and acting as a facilitator to strengthen the NLRP3-ASC-pro-caspase-1 interaction, promoting ASC oligomerization (activation). Consistently, in vivo studies demonstrate that Gal3-deficient mice exhibit significantly improved survival, reduced weight loss, and attenuated pulmonary inflammation and IL-1β release following infection, with the most pronounced protective effects observed against H5N1. Collectively, these findings identify Gal3 as a potent host factor that orchestrates excessive inflammation by simultaneously facilitating viral entry and driving the assembly of the NLRP3 inflammasome, highlighting the Gal3-NLRP3 axis as a promising therapeutic target to mitigate severe influenza-induced lung injury.

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with a broad spectrum of malignancies and immune-mediated disorders, and growing evidence highlights the importance of host glycan-lectin interactions in shaping viral persistence and immune escape. Among these, galectins have emerged as key regulators of the EBV life cycle, influencing viral attachment, latency maintenance, lytic reactivation, and the remodeling of the tumor microenvironment. Galectin-1, -3, and -9 exhibit context-dependent functions that collectively modulate oncogenic signaling pathways, T‑cell exhaustion, regulatory T‑cell expansion, and innate immune sensing. Recent clinical studies further suggest that circulating galectins and galectin-enriched exosomes may serve as non-invasive biomarkers for disease progression and prognosis in EBV-associated malignancies. Despite these advances, major knowledge gaps remain regarding member-specific functions, compensatory galectin networks, and the spatiotemporal dynamics of galectin regulation during infection. Targeting the galectin-glycan axis therefore represents a promising frontier for host-directed antiviral and anticancer therapies, with the potential to disrupt viral latency, restore antiviral immunity, and improve clinical outcomes in EBV-driven diseases.

The recent mpox outbreaks in non-endemic countries highlight the urgent need for improved therapeutics and diagnostics. In this study, monoclonal antibodies (mAbs) targeting the mpox enveloped virion antigens A35 and B6 were transiently expressed in Nicotiana benthamiana using a geminiviral vector system. Following agroinfiltration, anti-A35 and anti-B6 mAbs accumulated to 27 µg/g fresh weight at 3 days and 260 µg/g at 7 days post-infiltration, respectively. SDS-PAGE and Western blot analyses confirmed the assembly of antibodies, and the purified antibodies bound to mpox-infected Vero cells. The neutralization assays demonstrated moderate reductions in viral infection under the tested conditions. Additionally, an electrochemical immunosensor demonstrated the ability of plant-produced antibodies to detect mpox virus through antigen-antibody binding induced current changes. These results support that the plant-based systems as rapid platforms for producing mpox-specific antibodies for diagnostics and antiviral research.

BACKGROUND: Taiwan, a region traditionally considered non-endemic for dengue, experienced an unexpected and large-scale outbreak in 2023. We investigated the multifactorial drivers of this outbreak, including cross-border viral importation, serotype cocirculation, vector ecology, and climate variability.

METHODS: We analyzed national dengue surveillance data (2013-2023), meteorological records, and Breteau Index (BI) values, alongside molecular serotyping and whole-genome sequencing of clinical isolates. Time-lagged Poisson regression was used to identify predictors of indigenous dengue transmission in Kaohsiung and Tainan. Full-genome comparisons were conducted between 2023 strains and historical epidemic isolates.

RESULTS: A total of 26 706 laboratory-confirmed cases were reported, primarily in Tainan (80.7%) and Kaohsiung (11.9%). Real-time RT-PCR identified cocirculating DENV-1 and DENV-2 strains. Phylogenetic analysis confirmed the 2023 DENV-1 and DENV-2 strains were genetically linked to contemporary strains from Southeast Asian countries. Whole-genome sequencing identified several nonsynonymous mutations in the NS2A, NS3, and NS5 regions when compared with historical outbreak isolates. Time-lagged regression showed that imported cases, precipitation, and the BI were associated with incidence in univariate models. In Kaohsiung, the best-fitting multivariable model included the BI, but temperature and precipitation were the independent predictors. In Tainan, precipitation and, at longer lags, imported cases were more influential, while the BI lost significance after adjustment.

CONCLUSIONS: The 2023 dengue outbreak in Taiwan was driven by a complex interplay between viral introductions, climatic conditions, and vector dynamics. The differing transmission drivers observed between cities highlight the need for region-specific vector surveillance, climate-informed early warning systems, and sustained genomic monitoring to prevent future re-emergence of dengue in this non-endemic setting.

INTRODUCTION: Airborne particulate matter (PM), particularly fine (PM2.5) and coarse (PM10) particles, is a major environmental health concern linked to increased respiratory morbidity and mortality. During the COVID-19 pandemic, epidemiological studies suggested that PM exposure may worsen SARS-CoV-2 infection outcomes; however, cellular mechanisms underlying this association remain incompletely understood. Here, we investigated how pre-exposure to PM2.5 and PM10 impacts SARS-CoV-2 infection dynamics in Calu-3 human epithelial cells.

METHODS: Calu-3 cells were pre-exposed to PM for 72 h prior to infection with either the wild-type Wuhan strain or the more virulent Delta variant for additional 48 h. Viral infection, receptor expression, apoptosis and cytokine responses were assessed.

RESULTS: PM10, but not PM2.5, enhanced Delta variant infection, increasing the proportion of infected cells by 13.7% and viral titers by 2.6-fold compared with controls. This enhancement was not attributable to changes in ACE2 receptor expression or viral entry efficiency but instead impaired antiviral defenses. PM10 pre-exposure suppressed apoptosis and reduced the expression of pro-inflammatory cytokines including IFN-γ, IP-10, and TNF-α during Delta infection.

DISCUSSION: These findings suggest that PM10 compromise epithelial antiviral response by dampening apoptotic cell clearance and inflammatory responses, thereby creating a cellular condition more permissive to viral replication. Our study provides a mechanistic basis by which particulate air pollution may amplify SARS-CoV-2 pathogenicity in a variant-specific manner. These results underscore further validation in physiologically relevant systems and highlight the potential public health implications of air pollution during viral pandemics.

Originally identified in Kenya in 1921, African swine fever (ASF) primarily remained a sub-Saharan concern for nearly a century [...].

BACKGROUND: Taiwan experienced a major dengue outbreak in 2023 following the relaxation of COVID-19 border controls. The contributing factors remained unclear. This study investigated potential virological, immunological, and clinical drivers.

METHODS: We retrospectively analyzed laboratory-confirmed dengue virus (DENV) infections at a tertiary care hospital in southern Taiwan. Serotypes were identified by qRT-PCR. Viral origins were assessed through phylogenetic and envelope (E) gene amino acid analyses. Clinical features of DENV-1 and DENV-2 cases were compared. Neutralization and antibody-dependent enhancement (ADE) were evaluated using PRNT and ADE assays.

RESULTS: DENV-1 and DENV-2 were identified as the predominant circulating serotypes. Clinical analysis revealed that DENV-2 infection was significantly associated with older age, diabetes mellitus, hypertension, and elevated hematocrit levels (p < 0.05), and these associations remained statistically significant in multivariate analysis. Phylogenetic analysis showed that DENV-1 isolates belonged to genotypes I and IV, while DENV-2 strains were of the cosmopolitan genotype. These viruses clustered closely with strains from Southeast Asia. Amino acid analysis indicated that DENV-1 strains exhibited 2-10 substitutions relative to 2014 isolates, while DENV-2 strains closely matched those from 2015. Sera from the 2014-2015 outbreaks demonstrated potent homotypic but limited heterotypic neutralization. ADE was observed in heterotypic infection contexts.

CONCLUSIONS: The 2023 dengue outbreak in Taiwan was driven by co-circulation of DENV-1 and DENV-2, limited heterotypic immunity, and ADE. These findings highlight the importance of integrated virological surveillance, genotype monitoring, and immunological assessment to inform dengue control strategies in non-endemic regions experiencing imported viral threats.

BACKGROUND: Strengthening mRNA vaccine development in LMICs is essential for enhancing global pandemic preparedness. This study evaluated the safety and immunogenicity of Comvigen, a bivalent SARS-CoV-2 vaccine, in comparison to the Comirnaty bivalent vaccine (Comirnaty).

METHODS: This phase II, randomised, open-label, non-inferiority trial was conducted in Thailand across four centres. Participants (n = 450) were randomly assigned (2:1) to receive either Comvigen (50 μg) or Comirnaty (30 μg), using block randomisation (size = 9). Eligible participants had completed at least 2 doses of any approved COVID-19 vaccine, with the last mRNA-vaccine dose given over 3 months before enrolment. The non-inferiority margin of a geometric mean ratio (GMR) of 0.67. The primary immunogenicity endpoint was pseudovirus neutralisation titres (psVNT-50) against SARS-CoV-2 wild-type and Omicron BA.4/BA.5 at Day 29. Safety outcomes included local and systemic adverse reactions up to six months post-vaccination. Immunogenicity analyses were conducted on the Per-Protocol (PP) population and the modified Intent-to-Treat (mITT) population; safety analyses included all participants. Laboratory personnel were blinded to vaccine assignment (ClinicalTrials.gov: NCT05930730).

FINDINGS: Between October and November 2023, 450 participants were enrolled (median age of 36 years, IQR 30-45). At day 29, the geometric mean titre (GMT) of psVNT-50 against wild-type virus increased from 475.9 to 2062.9 for Comvigen and from 458.8 to 1905.1 for Comirnaty (GMR 1.1, 95% CI: 1.0-1.2), meeting non-inferiority criteria. Against Omicron BA.4/BA.5, GMTs were 3909.8 for Comvigen and 3288.6 for Comirnaty (GMR 1.2, 95% 1.0-1.4). Local and systemic reactions were more frequent with Comvigen (91% vs. 78%, p = 0.0002, 79% vs. 70%, p = 0.028) but were mild or moderate and transient with no difference in fever (6% vs. 5%, p = 0.84).

INTERPRETATION: Comvigen demonstrated non-inferiority immunogenicity to Comirnaty and had a comparable safety profile, supporting mRNA vaccine development for global access and pandemic preparedness.

FUNDING: Covid-19 Pandemic Emergency Fund granted by Thailand's National Economic and Social Development Council provided major funding. Supplementary funding was provided by National Vaccine Institute (NVI), Thailand; Center of Excellence in Vaccine Research and Development (Chula VRC), Faculty of Medicine, Chulalongkorn University; Chulalongkorn University Second Century Fund (C2F); BioNet-Asia and Public Donation through Covid-19 vaccine development fund of the Faculty of Medicine, Chulalongkorn University and the Thai Red Cross Society, Thailand.