Search Results (873)

Background: Preschool-aged children can have difficulty adhering to infection control measures and were affected during the Omicron wave of the coronavirus disease 2019 (COVID-19) pandemic. However, the impacts of prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination on viral load in this age group remain poorly understood. This study aimed to investigate the relationship between previous SARS-CoV-2 infection, COVID-19 vaccination, and viral load or clinical severity in preschool-aged children infected during the Omicron variant epidemic in Japan. Methods: This prospective observational study investigated 107 children aged 1–75 months who were diagnosed with COVID-19 between May and September 2023. Rapid antigen (Ag) tests were performed on days 1 and 5 or 6, and results were visually graded into four categories (–, ±, 1+, or 2+). Ag results were validated against quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) cycle threshold (Ct) values. Clinical parameters, including vaccination status, previous infection, age, maximum body temperature, and fever duration, were analyzed using multivariate regression models. Results: Higher Ag loads (1+/2+) were more frequently observed in younger children who had not experienced prior infection or full vaccination. Prior infection and vaccination were independently linked to lower Ag loads and reduced maximum body temperature. Many unvaccinated and infection-naïve children continued to show elevated Ag levels on day 5 or 6, corresponding to Ct values suggestive of potential infectivity. Conclusions: Prior SARS-CoV-2 infection and vaccination were linked to lower viral loads and milder febrile responses among preschool-aged children. These findings enhance our understanding of infection dynamics in this age group and may inform future discussions on public health strategies in pediatric settings. Full article

Porcine epidemic diarrhea virus (PEDV) is a primary pathogen responsible for viral diarrhea in swine. The identification of host resistance genes and key regulatory elements represents a critical prerequisite for developing novel control strategies. Krüppel-like factor 4 (KLF4), a multi-functional transcription factor, is known to regulate pathogenic infections; however, its specific roles in PEDV infection remain largely undefined. In this study, we found that KLF4 expression was upregulated following PEDV infection. Next, we constructed KLF4 knockout and overexpression cells and infected them with PEDV. The results show that viral RNA and protein expression levels and infectious viral titers were significantly enhanced in PEDV-infected KLF4 knockout cells compared to infected wild-type cells. In contrast, PEDV infection levels were significantly decreased in KLF4 overexpression cells relative to control cells. Transcriptomic analysis reveals that KLF4 significantly influences the expression of genes involved in key signaling pathways, including PI3K/Akt and MAPK. Overall, our findings elucidate the functional roles and underlying mechanisms of KLF4 during PEDV infection, offering valuable molecular targets for PEDV prevention and control. Full article

Despite the widespread accessibility of vaccines and antivirals, seasonal influenza virus epidemics continue to pose a threat to public health. In this study, we constructed a recombinant replication-deficient simian adenovirus type 25 vector carrying the full-length hemagglutinin (HA) of the H1N1 influenza virus, named rSAd25-H1. Both systemic and mucosal humoral immune responses, as well as the protective efficacy, were assessed in mice immunized via the intramuscular (IM) or intranasal (IN) route. A single-dose IM or IN administration of rSAd25-H1 elicited a robust systemic IgG antibody response, including hemagglutination inhibition antibodies. As expected, only IN immunization was able to induce IgA production in serum and respiratory mucosa. Notably, a single dose of rSAd25-H1 at the highest dose (10¹⁰ viral particles) conferred complete protection against lethal homologous H1N1 challenge in mice despite the route of administration. These findings demonstrate the potential of simian adenovirus type 25-based vectors as a promising candidate for intranasal vaccine development targeting respiratory pathogens. Full article

Background: Influenza viruses are major pathogens responsible for respiratory infections and pose significant risks to densely populated urban areas. RT-qPCR has made substantial contributions in controlling virus transmission during previous COVID-19 epidemics, but it faces challenges in terms of detection time for large sample sizes and susceptibility to nucleic acid contamination. Methods: Our study designed loop-mediated isothermal amplification primers for three common influenza viruses: A/H3N2, A/H1N1, and B/Victoria, and utilized a 4-channel microfluidic chip to achieve simultaneous detection. The chip initiates amplification by centrifugation and allows testing of up to eight samples at a time. Results: By creating a closed amplification system in the microfluidic chip, aerosol-induced nucleic acid contamination can be prevented through physically isolating the reaction from the operating environment. The chip can specifically detect A/H1N1, A/H3N2, and B/Victoria and has no signal for other common respiratory viruses. The testing process can be completed within 1 h and can be sensitive to viral RNA at concentrations as low as 10⁻³ ng/μL for A/H1N1 and A/H3N2 and 10⁻¹ ng/μL for B/Victori. A total of 296 virus swab samples were further analyzed using the microfluidic chip method and compared with the classical qPCR method, which resulted in high consistency. Conclusions: Our chip enables faster detection of influenza virus and avoids nucleic acid contamination, which is beneficial for POCT establishment and has lower requirements for the operating environment. Full article

Recent outbreaks of highly pathogenic human RNA viruses from probable zoonotic origin have highlighted the relevance of epidemic preparedness as a society. However, research in vaccinology and virology, as well as epidemiologic surveillance, is often constrained by the biological risk that live virus experimentation entails. These also involve expensive costs, time-consuming procedures, and advanced personnel expertise, hampering market access for many drugs. Most of these drawbacks can be circumvented with the use of pseudotyped viruses, which are surrogate, non-pathogenic recombinant viral particles bearing the surface envelope protein of a virus of interest. Pseudotyped viruses significantly expand the research potential in virology, enabling the study of non-culturable or highly infectious pathogens in a safer environment. Most are derived from lentiviral vectors, which confer a series of advantages due to their superior efficiency. During the past decade, many studies employing pseudotyped viruses have evaluated the efficacy of vaccines or monoclonal antibodies for relevant pathogens such as HIV-1, Ebolavirus, Influenza virus, or SARS-CoV-2. In this review, we aim to provide an overview of the applications of pseudotyped viruses when evaluating the neutralization capacity of exposed individuals, or candidate vaccines and antivirals in both preclinical models and clinical trials, to further help develop effective countermeasures against emerging neutralization-escape phenotypes. Full article

Background/Objectives: Moschus (musk) has long been used in traditional Tibetan medicine to prevent and treat epidemic febrile illnesses. However, its antiviral mechanisms remain poorly understood. Given the urgent need for effective treatments against viral respiratory tract infections (VRTIs), this study aimed to systematically investigate the molecular targets and pharmacological pathways through which Moschus may exert therapeutic effects. Methods: Based on the identification of bioactive compounds with favorable pharmacokinetics, we applied integrated network pharmacology and multi-omics analyses to systematically identify key therapeutic targets involved in VRTIs. Gene Set Enrichment Analysis (GSEA) and immune infiltration further revealed strong associations with multiple immune cell subsets, reflecting their pivotal roles in immunomodulatory mechanisms during viral infections. Molecular docking confirmed the strong binding affinities between Moschus compounds and these key targets. Results: Notably, testosterone exhibited the strongest and most consistent binding across key targets, suggesting its potential as a pivotal bioactive compound. Importantly, the antiviral effects of Moschus may be mediated in part by the downregulation of the key genes MCL1, MAPK3, and CDK2, which are involved in the regulation of viral replication, apoptosis, and host immune responses. Conclusions: This study provides a comprehensive mechanistic framework supporting the multi-target antiviral potential of Moschus, offering a scientific basis for its further development as a therapeutic agent against VRTIs. Full article

Culicoides (Diptera, Ceratopogonidae) are small biting midges and are known as vectors for many arboviruses, including bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV). Tengchong County of Yunnan Province, China, which borders Myanmar, has many private farms with goats, sheep, and cattle. To estimate the risk of Culicoides-borne viral diseases such as bluetongue (BT) and epizootic hemorrhagic disease (EHD) in this area, an investigation of the diversity and abundance of Culicoides in Tengchong between May 2024 and April 2025 was performed. As a result, 70 collections totaling approximately 93,000 Culicoides were carried out at five farms (cattle + Asian buffaloes, goats, and sheep, respectively). Nineteen species were identified, and eight potential cryptic species were found. A total of 13 cox1 sequences and 4 28S sequences for 13 specimens were generated. The most dominant species were Obsoletus (44.1%), C. homotomus (23.3%), and C. arakawae (12.9%) at the bovine farm; C. tainanus (68.0%), C. orientalis (12.6%), and C. newsteadi (Asia) (6.3%) at the goat farm; and C. tainanus (73.6%), C. fenggangensis (7.3%), and C. sp. nr palpifer (6.3%) at the sheep farm. In this investigation, C. tainanus, Obsoletus, and C. orientalis were the most dominant potential BTV vectors, and the period between July and October may be the main period for epidemics of Culicoides-borne viruses in Tengchong. Full article

The seasonal patterns of viral diseases in farm animals present significant challenges to global livestock productivity, with cold stress emerging as a potential modulator of host–pathogen interactions. This review synthesizes current knowledge on the expression dynamics of heat shock protein 70 (HSP70) in farm animals under cold-stress conditions and its potential roles as (1) a viral replication facilitator and (2) an immune response regulator. This review highlights cold-induced HSP70 overexpression in essential organs, as well as its effects on significant virus life cycles, such as porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), and bovine viral diarrhea virus (BVDV), through processes like viral protein chaperoning, replication complex stabilization, and host defense modulation. By integrating insights from thermophysiology, virology, and immunology, we suggest that HSP70 serves as a crucial link between environmental stress and viral disease seasonality. We also discuss translational opportunities targeting HSP70 pathways to break the cycle of seasonal outbreaks, while addressing key knowledge gaps requiring further investigation. This article provides a framework for understanding climate-driven disease patterns and developing seasonally adjusted intervention strategies. Full article

Porcine epidemic diarrhea virus (PEDV) infection induces severe, often fatal, watery diarrhea and vomiting in neonatal piglets, characterized by profound dehydration, villus atrophy, and catastrophic mortality rates approaching 100% in unprotected herds. This study developed a composite probiotic from Min-pig-derived Lactobacillus crispatus LCM233, Ligilactobacillus salivarius LSM231, and Lactiplantibacillus plantarum LPM239, which exhibited synergistic growth, potent acid/bile salt tolerance, and broad-spectrum antimicrobial activity against pathogens. In vitro, the probiotic combination disrupted pathogen ultrastructure and inhibited PEDV replication in IPI-2I cells. In vivo, PEDV-infected piglets administered with the multi-strain probiotic exhibited decreased viral loads in anal and nasal swabs, as well as in intestinal tissues. This intervention was associated with the alleviation of diarrhea symptoms and improved weight gain. Furthermore, the multi-strain probiotic facilitated the repair of intestinal villi and tight junctions, increased the number of goblet cells, downregulated pro-inflammatory cytokines, enhanced the expression of barrier proteins, and upregulated antiviral interferon-stimulated genes. These findings demonstrate that the multi-strain probiotic mitigates PEDV-induced damage by restoring intestinal barrier homeostasis and modulating immune responses, providing a novel strategy for controlling PEDV infections. Full article

Viral conjunctivitis is a highly contagious ocular condition that significantly impacts patient quality of life and healthcare resources. Despite its self-limiting nature, the condition remains a significant public health concern due to its high transmissibility, prolonged symptoms, and potential complications such as subepithelial infiltrates (SEIs). This review aimed to synthesize and evaluate current management strategies for adenoviral conjunctivitis and provide an evidence-based treatment framework. A systematic literature search of PubMed and the Cochrane Library was conducted, identifying 25 eligible studies published between 2009 and 2024 that focused on clinical interventions including supportive care, antiseptics, corticosteroids, antivirals, and immune modulators. The findings indicate that while supportive therapy and hygiene measures remain central to care, antiseptic agents, specifically povidone–iodine, and topical steroids offer additional benefit in reducing symptom duration and complications. Combination therapies integrating antiseptics, corticosteroids, and immunomodulators show promise for more severe cases, especially those complicated by SEIs. This review proposes an evidence-based comprehensive, multimodal approach management algorithm while highlighting the need for future research in antiviral development and diagnostic innovation to avoid mistreatment and unnecessary antibiotic use. Full article

The 2016 Zika virus (ZIKV) epidemic has largely subsided, but a key question remains. How did ZIKV evolve to become a virulent human pathogen compared to the virus of its original discovery? What specific virologic and pathologic changes contributed to increased pathogenicity in humans? Phylogenetic studies have identified two genetically distinct ZIKV, the African and Asian lineages, which differ in their pathogenicity. Previous studies including ours suggest that the envelope (E) protein plays a key role in viral entry, immune activation, and neuropathogenesis. This study aimed to further elucidate virologic and pathogenic differences between these lineages by assessing their ability to bind and replicate in host cells, induce apoptotic cell death, trigger inflammatory responses, and influence human neural progenitor cell (hNPC)-derived neurosphere formation. We compared a historic African ZIKV strain (MR766) with an epidemic Brazilian strain (BR15) and evaluated the effects of the E protein inhibitor quercetin-3-β-O-D-glucoside (Q3G) and an E protein-neutralizing antibody (AbII). Our results revealed distinct virologic properties and that MR766 exhibited stronger inhibition of neurosphere formation due to enhanced viral binding to neuronal SH-SY5Y cells, while BR15 infection triggered a heightened pro-inflammatory cytokine response with reduced viral binding. Chimeric virus studies suggested that the E protein likely influences viral binding, replication efficiency, immune activation, and neuropathogenesis. Notably, Q3G exhibited antiviral activities against both MR766 and BR15, whereas AbII preferentially inhibited MR766. These findings highlight the virological differences between ancestral and epidemic viral strains, as well as the critical role of E protein in viral permissiveness, immune response, and neuropathogenesis, providing insights for developing targeted antiviral strategies. Full article

Avian influenza virus (AIV) remains a persistent threat to both the poultry industry and human health. Among the AIV subtypes posing public health threats, H7N9 AIV is responsible for five epidemic waves of human infection in China. Here, a detection system based on a mouse model was established, which can simultaneously and quantitatively analyze the dynamic changes in the viral genomic RNA (vRNA), complementary RNA (cRNA), and messenger RNA (mRNA) of H7N9 AIV by using reverse transcription primers with tag sequences to reverse transcribe the three species of RNAs into corresponding cDNA templates, which are then absolutely quantified using the TaqMan quantitative PCR method. This system specifically targets the PB2 and NA genes and, for the first time, enables a spatiotemporal analysis of all three viral RNA species within an animal model. Our results revealed that H7N9 AIV exhibits characteristic replication kinetics, with all three species of viral RNAs showing a rapid increase followed by a certain degree of decline. This system offers a powerful tool for us to further advance our understanding of the replication dynamics of AIV in mice. Full article

Porcine rotavirus (PoRV), a primary etiological agent of viral diarrhea in piglets, frequently co-infects with other enteric pathogens, exacerbating disease severity and causing substantial economic losses. Its genetic recombination capability enables cross-species transmission potential, posing public health risks. Globally, twelve G genotypes and thirteen P genotypes have been identified, with G9, G5, G3, and G4 emerging as predominant circulating strains. The limited cross-protective immunity between genotypes compromises vaccine efficacy, necessitating genotype surveillance to guide vaccine development. While conventional molecular assays demonstrate sensitivity, they lack rapid genotyping capacity and face technical limitations. To address this, we developed a novel diagnostic platform integrating reverse transcription recombinase-aided amplification (RT-RAA) with CRISPR–Cas12a. This system employs universal primers for the simultaneous amplification of G4/G5/G9 genotypes in a single reaction, coupled with sequence-specific CRISPR recognition, achieving genotyping within 50 min at 37 °C with 10⁰ copies/μL sensitivity. Clinical validation showed a high concordance with reverse transcription quantitative polymerase chain reaction (RT-qPCR). This advancement provides an efficient tool for rapid viral genotyping, vaccine compatibility evaluation, and optimized epidemic control strategies. Full article

The novel goose parvovirus (NGPV) and the novel duck reovirus (NDRV) are pathogens that can substantially affect the growth and development of ducklings, causing considerable economic losses to duck farms. Therefore, a timely, rapid, accurate, and high-throughput diagnosis and identification of viral infections are critical for preventing the spread of epidemics. In this study, a TaqMan probe-based duplex one-step RT-qPCR was established for the simultaneous detection and qualitative and quantitative identification of the two viruses. It demonstrated greater sensitivity than conventional PCR, detecting as low as 2.42 copies/μL of NGPV genome and 70.1 copies/μL of NDRV genome. Additionally, it exhibited remarkable specificity, responding exclusively to the nucleic acids of target pathogens. It also demonstrated excellent reproducibility and availability, particularly in clinical settings, with a coinfection detection rate of 13.3%, contributing to the development of NGPV- and NDRV-testing technologies. Full article

Over the past decade, diseases associated with fowl adenoviruses (FAdVs) have exhibited a new epidemic trend worldwide. The presence of numerous FAdVs serotypes, combined with the virus’s broad host range, positions it as a significant pathogen in the poultry industry. In the current context of intensive poultry production and global trade, co-infections involving multiple FAdVs serotypes, as well as co-infections with FAdVs alongside infectious bursal disease or infectious anemia virus, may occur within the same region or even on the same farm. The frequency of these outbreaks complicates the prevention and control of FAdVs. Therefore, the development of effective, targeted vaccines is essential for providing technical support in the management of FAdVs epidemics. Ongoing vaccine research aims to improve vaccine efficacy and address the challenges posed by emerging FAdVs outbreaks. This review focuses on vaccines developed and studied worldwide for various serotypes of FAdVs in the past decade. It encompasses inactivated vaccines, live attenuated vaccines, e.g., host-adapted attenuated vaccines and gene deletion vaccines, viral vector vaccines, and subunit vaccines (including VLP proteins and chimeric proteins). The current limitations and future development directions of FAdVs vaccine development are also proposed to provide a reference for new-generation vaccines and innovative vaccination strategies against FAdVs, as well as for the rapid development of highly effective vaccines. Full article