Search Results (3,780)

Herpes simplex virus 1 (HSV-1) is a rare cause of acute hepatitis, especially in patients with chronic immunosuppression. We performed whole-genome HSV-1 sequencing with a metagenomics approach on peripheral blood samples from an Italian case of fatal acute liver failure with high circulating HSV-1 (1,129,900,000 copies/mL), followed by phylogenetic analysis. After multiple sequence alignment, a final dataset of 182 whole-genome sequences was selected. The sequenced HSV-1 strain belonged to a phylogenetic clade isolated in Florida in 2002 (OQ724868.1). A characterization of single nucleotide polymorphisms and indels was performed to determine their effects on the viral genome: only one variant, classified as an indel, was detected with a high impact effect (c.905_906insGTTTT) in the UL49A gene, which is known to encode a membrane protein regulating virion morphogenesis, replication and assembly. In addition, this study also detected variants in other genes involved in crucial steps of the HSV-1 life cycle, like alpha-regulation (US7), capsid transport (UL36) and viral polymerase function (UL30). In conclusion, the results of this variant analysis confirmed that in HSV-1 hepatitis, some viral regions may be hotspots for adaptive mutations with a substantial impact on viral replication or immune evasion. Full article

Human papillomavirus (HPV) infection is a major driver of anogenital disease and virus-related carcinogenesis. Although most infections resolve spontaneously, persistent infection with high-risk genotypes may progress to high-grade squamous intraepithelial lesions (HSILs) and cancer, particularly in the setting of impaired immune surveillance. Unlike previous HPV-related reviews focused primarily on cervical disease, vaccination, or isolated immunosuppressed populations, this narrative review comparatively examines the clinical expression, colposcopic findings, screening strategies, and therapeutic implications of HPV-related disease across the immunological spectrum. This narrative review provides an integrative synthesis of HPV-related disease in the female lower genital tract across the immunological spectrum. A structured, non-systematic search of PubMed/MEDLINE, Scopus, and Web of Science was conducted using terms related to “human papillomavirus”, “HPV”, “cervical intraepithelial neoplasia”, “colposcopy”, “immunosuppression”, “HIV”, and “vaccination”. Immunosuppressed populations, including individuals living with HIV, transplant recipients, and patients receiving immunosuppressive therapy, exhibit higher rates of persistent infection, multifocal disease, recurrence, and progression to HSIL and invasive malignancy. These patients also present greater diagnostic complexity, broader anatomical involvement, and reduced response to conventional treatment. Rather than representing a uniform condition, HPV-related disease reflects a biologically dynamic spectrum shaped by host immune competence. This review highlights the distinct clinical, colposcopic, and therapeutic challenges observed in immunosuppressed populations and reinforces the need for individualized, risk-adapted strategies integrating contemporary advances in screening, vaccination, and HPV-related disease management. Full article

High-throughput sequencing methods have made it possible to identify numerous novel tick-borne viruses that are potentially pathogenic to humans. Among these, Songling virus (Orthonairovirus songlingense, SGLV) has been associated with febrile illness in patients following tick bites in China, but its geographic distribution outside China remains largely unexplored. In this study, we aimed to detect SGLV circulation in ticks across Asian Russia, focusing on regions bordering China. A total of 3444 adult ticks representing six species were collected from 170 locations across 11 regions during the summer of 2024. SGLV RNA was detected in Haemaphysalis concinna ticks, with 11 positive specimens yielding an SGLV RNA prevalence rate of 2.2%. Positive ticks were found in four regions, with the highest positivity rate (5.8%) recorded in Amur Oblast, which directly borders China. The detection of SGLV in the Republic of Altai represents the westernmost record of this virus to date. Full-length nucleoprotein-coding sequences obtained for all Russian isolates revealed up to 1.2% nucleotide divergence. Phylogenetic analysis confirmed that all Russian SGLV isolates belong to Orthonairovirus songlingense, with the Altai SGLV isolate showing genetic similarity to a human-derived Chinese SGLV isolate. Co-infections with Rickettsia heilongjiangensis were detected in four SGLV-positive ticks, highlighting the potential for simultaneous pathogen transmission. These findings establish the first evidence of SGLV circulation in Russia across a wide geographic range and underscore the need for differential diagnosis of febrile illnesses following tick bites in this region. Full article

H9N2 avian influenza viruses inherently carry cross-species transmission potential, making continuous surveillance critical for pandemic prevention. This study focused on monitoring the 2024 H9N2 epidemic in Jiangsu Province’s external environment, analyzing its molecular evolution and receptor binding properties, assessing cross-species transmission and pandemic risks, and investigating serological antibody levels across different human populations. Environmental samples were collected from live poultry markets, farms, slaughterhouses, and bird habitats across Jiangsu, screened via quantitative PCR (qPCR), with positive samples used for virus isolation and whole-genome sequencing. Receptor binding properties were tested by hemagglutination assay, and H9N2 antibody levels were measured in 370 occupationally exposed individuals and 240 non-exposed individuals using hemagglutination inhibition (HI) assays. Among the 5779 collected samples, 6.89% tested H9N2-positive, and 12 strains belonging to the Eurasian lineage Y280-like clade G57 genotype were successfully isolated. All strains carried the HA-Q226L mutation, with 11 showing preferential binding to human α-2,6 receptors and one strain possessing dual receptor binding capability. Internal genes harbored mammalian adaptation mutations, and M2 proteins contained mutations conferring complete resistance to amantadine-class antiviral drugs. Serological tests revealed antibody positive rates of 4.05% in exposed populations and 2.5% in non-exposed populations, with no statistically significant difference between groups. These findings confirm that Jiangsu’s circulating H9N2 viruses have acquired human receptor preference and mammalian adaptation, posing silent infection and pandemic risks. Enhanced surveillance and the development of candidate vaccine stockpiles are strongly recommended. Full article

Porcine reproductive and respiratory syndrome (PRRS), caused by PRRS virus (PRRSV), poses a serious threat to the global swine industry. Although modified live virus (MLV) vaccines have been widely used in the field for PRRS prevention for decades, the safety and efficacy of these vaccines have long been controversial. Here, we report a rare recombination pattern in China: the emergence of a novel NADC30-like PRRSV strain recombined from two MLV-like strains. Genome comparative analysis reveals that the SCMS2025 isolate has a non-continuous 136-amino acid deletion in the NSP2 protein and shares the highest nucleotide identity of 87.6% with lineage 5 (L5) strains. Phylogenetic analysis showed that SCMS2025 was classified into L1 (NADC30-like) strains based on ORF5 genotyping, whereas it belonged to a single branch between L1 and L5 strains based on the complete genomic sequences. Strikingly, genomic recombination analysis revealed that the newly emerged PRRSV isolate likely resulted from complex recombination events between NADC30-like and two MLV-like strains (RespPRRS MLV and TJbd14-1 MLV-like strains). Furthermore, SCMS2025 infection caused transient overt clinical signs followed by rapid recovery, indicating that the novel PRRSV isolate is a low pathogenic strain. Notably, all SCMS2025-inoculated piglets remained seronegative for PRRSV-specific antibodies throughout the entire 14-day observation period, suggesting a delayed onset of the host humoral immune response. Our study provides evidence for the ongoing evolution of PRRSV through inter lineage recombination and highlights the urgent need for safe and effective vaccines. Full article

The genetic and antigenic diversity of H5Nx HPAI Gs/GD lineage continues to be a great challenge facing conventional inactivated vaccines. To overcome this challenge, a recombinant herpes virus of turkey (rHVT) vaccine expressing the viral protein 2 (VP2) of infectious bursal disease (IBD) and H5, rHVT+IBD+H5, was developed using computationally optimized broadly reactive antigen (COBRA) technology. In the current study, the protective efficacy of a commercially available vector trivalent vaccine rHVT+IBD+H5 using COBRA technology was assessed. A total of 120 commercial broilers were divided equally into six groups (G1B–G6B). The chickens in G1B–G3B were challenged with the most recent circulating HPAI-H5N1 clade 2.3.4.4.b Egyptian isolate (GenBank accession No. OQ933425) at 28 days old (DO), while the chickens in G4B and G5B were kept as vaccinated (as G1B and G2B, respectively) and non-challenged, and G6B was the non-vaccinated non-challenged group. In G1B, the chickens were vaccinated with Vaxxitek^® rHVT+IBD+H5 at 1 DO and boostered with a commercially available subunit Baculovirus bivalent inactivated H5+ND (Volvac^® B.E.S.T AI+ND) at 10 DO and had a 100% survival rate. The standalone vaccinated chicken G2B, using rHVT+IBD+H5 at 1 DO, had a highly significant survival rate (90%) vs. 0% (100% mortality) in the non-vaccinated challenged control, G3B. All the vaccinated groups had higher seroconversion at 45 DO especially using H5-coated antigen plates for the enzyme-linked immunosorbent assay (ELISA) test. The viral shedding titers and time were evaluated using a quantitative real-time polymerase chain reaction (RT-qPCR) in the collected oropharyngeal and cloacal swabs at 3, 5, 7, and 10 days post-challenge (DPC). In conclusion, vaccination with rHVT+IBD+H5 either as a standalone or when boostered with subunit Baculovirus bivalent inactivated ND+H5 resulted in 90 and 100% protection, respectively, without significant difference in the quantity and duration of viral shedding between both groups against HPAI-H5N1 clade 2.3.4.4.b experimental challenge in broilers. Full article

Background/Objectives: Mosquitoes, including Culex quinquefasciatus and Aedes aegypti, are important vectors of dengue fever, Zika virus, West Nile virus, Japanese encephalitis virus, Eastern equine encephalitis virus, etc. Biological control has always been urgent in mosquito prevention due to resistance developing to synthetic insecticides and environmental toxicity by insecticides. Methods: The leaf essential oil of Mosla. chinensis was isolated, and major components were identified via GC-MS, followed by olfactory behavior assays to evaluate its repellent activity against C. quinquefasciatus. Additionally, the odorant-binding protein 1 and odorant-binding protein 2 (CquiOBP1-2) genes were prokaryotically expressed, and their fluorescence competitive binding activities with the active components of essential oils were examined. Results: The bioassays indicated this essential oil greatly repels C. quinquefasciatus, which will significantly protect people against vector-borne diseases. In the fluorescence competitive binding experiments, the CquiOBP1-2 proteins exhibit great binding capacities to volatile components, including Citronellal, Citronellol, Geraniol, Limonene and Isopulegol. Furthermore, the behavioral experimental results also indicate that the mixture of these five ligand compounds has an obvious repellent effect on mosquitoes, highlighting that they may be applied as potential mosquito repellent agents. Moreover, molecular docking and site-directed mutation analysis further confirm Phe123 and Gln77 are both key amino acid residues of CquiOBP1-2 proteins involved in the olfactory recognition of repellent ligand compounds from M. chinensis essential oil. Conclusions: The behavioral experimental verification and the exploration of olfactory molecular mechanisms are helpful to promote the biological control of plant essential oils in mosquito pests. Full article

Gastrointestinal symptoms (GI) (abdominal pain, vomiting, and diarrhea) during the febrile phase of dengue (less than 5 days from fever onset) might indicate prominent innate immune responses. Serum and feces samples from cases with GI symptoms versus those without GI symptoms (n = 20 per group) were analyzed. From these, only the neutrophil extracellular traps (NETs), serum fibroblast growth factor (FGF) 21, and fecal microbiome analyses, but not the routine parameters, endotoxemia, or serum cytokines, were higher in the GI cases than in the non-GI cases. From the in vitro experiments, both lipopolysaccharide (LPS) and the dengue virus (DENV) upregulated the FGF receptor 1 (FGFR1) and cytokines in hepatocytes (HepG2) and THP-1-differentiated macrophages. Meanwhile, LPS and DENV induced NETs in isolated neutrophils from healthy volunteers. Only the starvation protocol, but not LPS or DENV, enhanced supernatant FGF-21 from hepatocytes. Incubation of recombinant FGF-21 in LPS + DENV-activated cells (hepatocytes, macrophages, and neutrophils) attenuated inflammation, as determined by supernatant cytokines and NETs. Hence, abdominal symptoms in dengue during the febrile phase indicate prominent innate immune responses, as detected by NETs and FGF-21 (an acute-phase protein), implying significant hepatic stress with a possible counteracting anti-inflammation. Full article

The Yezo virus (YEZV) is a recently discovered tick-borne orthonairovirus with pathogenic potential, causing acute febrile illness in humans. Viral nucleoproteins (N) play a key role in genome packaging, replication, and modulation of host immune responses, making their structural characterization essential for understanding viral pathogenesis and developing targeted countermeasures. However, the absence of structural data for YEZV proteins significantly hinders these efforts. This study presents the first solution structure of the YEZV N domain 1 (D1). A highly purified, soluble, tag-free recombinant YEZV N D1 was produced from the native sequence of the clinical YEZV isolate. The native-state conformation was resolved through an integrated approach combining size-exclusion chromatography coupled with small-angle X-ray scattering (SEC-SAXS), AlphaFold 3 structure prediction, and all-atom molecular dynamics simulations. The YEZV N D1 structure adopts a stable, predominantly α-helical globular fold that remains monomeric under near-physiological conditions. SEC-SAXS data show excellent agreement with computational models, revealing moderate conformational flexibility. The characterized recombinant YEZV N D1 and its first solution structure reported here providing essential insights into understanding of YEZV molecular architecture. These findings lay a foundation for rational serological assay development and structure-guided therapeutic design against this and other emerging orthonairoviruses. Full article

Background/Objectives: Arboviral diseases transmitted by Aedes mosquitoes, including Dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV), represent a major public health challenge in tropical regions. Their clinical similarity complicates differential diagnosis, particularly in settings of viral co-circulation, and may lead to underdiagnosis. The objective was to detect acute dengue infection and assess serological evidence of Chikungunya and Zika virus exposure among patients with acute febrile syndrome and clinical suspicion of dengue in the department of Córdoba, Colombia. Methods: A prospective descriptive study was conducted between 2023 and 2024 in healthcare institutions in Montería and Sahagún. Serum samples were analyzed by ELISA to detect DENV NS1 antigen, anti-CHIKV IgM, and anti-ZIKV IgG antibodies. Sociodemographic, clinical, and laboratory variables were described, and the association between prior ZIKV infection and dengue severity was assessed. Results: Ninety patients were included. Isolated laboratory marker detection was observed for DENV NS1 antigen in 36.7% (33/90), anti-ZIKV IgG in 30.0% (27/90), and anti-CHIKV IgM in 2.2% (2/90); combined arboviral markers were identified in 22.2% (20/90), and 8.9% (8/90) had no detectable markers. Among NS1-confirmed dengue cases (n = 47), 61.7% (29/47) were classified as dengue with warning signs. Anti-ZIKV IgG detection was not associated with dengue clinical classification (p = 0.989), although platelet counts were lower in IgG-positive cases (p = 0.037). Conclusions: The findings support laboratory-supported diagnosis and integrated acute febrile illness surveillance in Córdoba, including locally adapted vector control, in a setting of arbovirus co-circulation with overlapping laboratory markers. Full article

Tobacco streak virus (TSV) has a wide range of natural host plants, yet it has not been detected in plants of the Arecaceae family. In Hainan, China, areca plants exhibited yellow-green chlorotic streaked leaves, and irregular chlorotic patches appeared on the main stem, which collectively represents typical TSV-infection symptoms. In this study, the near-complete genome sequence of the TSV A6-5 isolate was obtained through meta-transcriptome sequencing combined with reverse transcription polymerase chain reaction (RT-PCR). Molecular characterization indicated that its RNA1 (3435 nt), RNA2 (2841 nt), and RNA3 (2193 nt) shared 99.27%, 99.16% and 98.40% nucleotide sequence identity, respectively, with the previously documented TSV DSMZ PV-0612 isolate from Rudbeckia sp. in Germany. No recombination signals were detected in the RNA1, RNA2, and RNA3 sequences of the TSV A6-5 isolate using all algorithms embedded in RDP5, indicating the isolate is highly evolutionarily conserved. Furthermore, phylogenetic analyses based on the full-length sequences of RNA1, RNA2 and RNA3 collectively verified that the TSV A6-5 is most closely related to TSV DSMZ PV-0612. This study documents the first case of natural TSV infection in Areca catechu L. worldwide and provides a theoretical foundation for the monitoring and control of TSV in areca palm production. Full article

Neuronal senescence-like states are increasingly implicated in age-related neurodegeneration, yet the neuron-intrinsic regulators that drive these phenotypes remain poorly defined. Guided by prior transcriptomic analysis of aged basal forebrain cholinergic neurons, we investigated Srebf2 and Zmiz1 using primary basal forebrain neuronal cultures with adeno-associated virus-mediated gain- and loss-of-function, quantitative immunocytochemistry, and low-input transcriptomic profiling of fluorescence-activated cell sorting-isolated neurons. Both perturbation strategies produced the expected directional changes in target transcripts. Overexpression of either gene increased the other, whereas knockdown did not elicit reciprocal suppression, indicating asymmetric regulatory coupling. Phenotypically, Srebf2 showed a bidirectional association with senescence-like changes, as both overexpression and knockdown increased p16 and p21, whereas Zmiz1 acted more directionally, with overexpression increasing and knockdown reducing these markers. Transcriptomic profiling revealed broad direction-dependent remodeling, including a set of 55 genes that changed concordantly across perturbation directions. Pathway analysis further showed specialization, with Zmiz1 preferentially associated with an Alzheimer’s disease-related signature and Srebf2 more strongly linked to cholinergic synapse programs. Together, these findings identify Srebf2 and Zmiz1 as coupled but non-equivalent regulators of a neuronal senescence-like program. Full article

Objectives: Noninvasive prenatal testing relies on the analysis of total cell-free DNA (cfDNA) in maternal plasma, where fetal-derived DNA constitutes only a minor fraction. This study aimed to preliminarily compare a modified TPY cfDNA extraction protocol with two commercial extraction kits for the downstream detection of Y-chromosome-specific markers in pregnancies carrying male fetuses. Methods: Plasma samples were obtained from 52 singleton pregnancies between 10 and 30 weeks of gestation with male fetal sex confirmed by ultrasonography. Total cfDNA was extracted from aliquots of the same maternal plasma samples using the modified TPY protocol, the QIAamp DSP Virus Kit, and the MagMAX™ Cell-Free DNA Isolation Kit. Quantitative real-time PCR was performed for the Y-chromosome-specific markers SRY and DYS14. At the same time, GLO was used as a reference marker to reflect the total cfDNA background. Extraction performance was assessed primarily using total cfDNA concentration and Ct values obtained from amplification of fetal-specific Y-chromosome markers. Results: Total cfDNA concentrations varied among the extraction methods, with the commercial kits yielding higher total cfDNA concentrations than the modified TPY protocol. In contrast, the TPY protocol yielded slightly lower mean Ct values for SRY and DYS14 than the commercial kits. SRY and DYS14 amplification was detected in 90.4% and 94.2% of samples, respectively. However, these Ct differences should be interpreted cautiously because fetal fraction, maternal DNA contamination, extraction recovery, and fragment size distribution were not directly measured. Conclusions: The modified TPY protocol showed preliminary technical feasibility for extracting total cfDNA from maternal plasma and enabling downstream amplification of Y-chromosome-specific markers in male pregnancies. Nevertheless, the observed lower Ct values do not establish selective fetal DNA enrichment, reduced maternal DNA contamination, or clinical superiority over commercial methods. Further analytical validation using standardized fetal fraction measurement, recovery efficiency testing, fragment size analysis, fetal-to-maternal DNA ratio assessment, and larger cohorts including both male and female pregnancies is required before broader clinical applicability can be determined. Full article

Angelica dahurica (A. dahurica) is an important medicinal plant in China; however, its production is affected by viral infections, leading to reduced yields and quality. In this study, we identified a novel carlavirus, tentatively named Angelica carlavirus virus (AnCV), in the leaves of A. dahurica exhibiting mosaic and leaf crinkling symptoms. Notably, the complete genome of AnCV was 8562 nt long and contained six open reading frames, with a genomic organization typical of the genus Carlavirus. AnCV exhibited 44.5–57.8% nucleotide identity at the whole-genome level with known members of the genus Carlavirus. In the polymerase gene and coat protein regions, the highest nucleotide and amino acid identities were 59.4–60.0% and 46.5–55.8%, respectively, which were below the species demarcation criteria established by the International Committee on Taxonomy of Viruses for the genus Carlavirus. Importantly, 10 AnCV isolates clustered within subgroup I of the genus Carlavirus, forming a relatively distinct branch. Moreover, 119 of the 280 A. dahurica samples were positive for AnCV (detection rate of 42.58%). Our study revealed that AnCV is a novel member of the genus Carlavirus that infects A. dahurica, providing a theoretical basis for the monitoring and control of viral diseases in A. dahurica. Full article

Background/Objectives: Wound infections represent a major category of healthcare-associated infections (HAIs) that interrupt the wound healing process, resulting in delayed wound healing and increasing the incidence of mortality, morbidity and healthcare costs. With the emergence of antibiotic resistance, there is an urgent need to find alternative therapeutic strategies capable of overcoming antibiotic resistance while simultaneously promoting wound healing. Previously, we synthesized iron oxide nanoparticles stabilized with cetyltrimethylammonium bromide (IONPs-CTAB), reported their antimicrobial activity against selected multidrug-resistant bacteria (MDR-bacteria) and SARS-CoV2 virus, and addressed their biocompatibility with the skin and eyes of rabbits. Therefore, it is hypothesized that IONPs-CTAB might be a promising alternative therapeutic agent for management of infected wounds. Methods: IONPs-CTAB were synthesized, and their successful synthesis was confirmed by FTIR, DSC-TGA, and XPS. Their antibacterial activity against three MDR-bacteria, Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), isolated from infected wounds was investigated via the microdilution test to determine MIC/MBC, and a time–kill curve study was also performed. Subsequently, an in vivo study was conducted to assess their wound healing activity on both non-infected and infected wounds. Results: IONPs-CTAB had MIC and MBC values ranging from 125 to 250, and 500 to 1000 µg/mL, respectively. The time–kill curve study showed an effective control of bacterial growth for all tested bacteria. The vivo study demonstrated the superior wound healing activity of IONPs-CTAB compared to standard treatment on both non-infected and infected wounds. This was further confirmed by histopathological examination and biochemical analysis. Conclusions: IONPs-CTAB might be a good therapeutic alternative for the management of infected and non-infected wounds. However, future studies are still required to assess their long-term safety and the possibility of their extravasation to systemic circulation, with their potential accumulation in various organs after a long-term application. Full article