Search Results (441)

Feline calicivirus (FCV) is a highly heterogeneous pathogen and a major cause of feline upper respiratory tract disease, highlighting the need for continuous surveillance of its genetic diversity and pathogenic characteristics. In this study, we isolated and comprehensively characterized a newly isolated FCV strain, HN/ZZ/2025, from cats at a feline trading market in Zhengzhou, China, and systematically evaluated its molecular features, in vitro replication characteristics, physicochemical properties, and pathogenicity in cats. Phylogenetic analysis classified HN/ZZ/2025 as genotype GI. The isolate replicated efficiently in CRFK, F81, and Fc3Tg cells, reaching peak titers of 10^7.18, 10^7.50, and 10^5.89 TCID₅₀/0.1 mL, respectively, and exhibited typical calicivirus-like particles with diameters of 35–40 nm. Complete genome analysis showed that HN/ZZ/2025 shared the highest nucleotide and amino acid sequence identities of 85.7% and 62.8%, respectively, with the closely related Chinese FCV strain CH-JL4, and revealed distinct amino acid variations within the hypervariable E region of the VP1 capsid protein. Experimental infection of cats (n = 3/group) resulted in pyrexia, with rectal temperatures reaching 39.8–40.2 °C, weight loss, oral ulceration, and persistent viral RNA shedding from 1 to 21 days post-infection. Viral RNA and VP1 antigen were detected in the lungs, trachea, kidneys, and spleen, indicating systemic dissemination and broad tissue distribution. Although no mortality occurred during the observation period, the observed clinical signs, viral dissemination, and histopathological lesions indicate that HN/ZZ/2025 is capable of causing clinically evident disease in experimentally infected cats. These findings provide useful insights into the molecular epidemiology, tissue tropism, and host–virus interactions of circulating FCV strains and establish HN/ZZ/2025 as a useful isolate for future studies of FCV genetic diversity and pathogenesis. Full article

Nipah virus (NiV) is a single-stranded negative-sense RNA virus of the genus Henipavirus, family Paramyxoviridae. The World Health Organization has declared NiV a priority pathogen with a great public health risk due to its epidemic potential and lack of sufficient countermeasures. In humans, the virus causes Nipah viral disease (NVD), characterized by acute respiratory failure and/or encephalitis. Long-term assessments of NVD survivors have revealed persistent neurological dysfunction, including encephalopathy, cerebral atrophy, hyperintensities, ocular motor palsies, and dystonia. The entry of NiV into the central nervous system (CNS) is one of the critical and less studied aspects of its pathogenesis. NiV rapidly targets the olfactory epithelial cells in the nasal turbinate and subsequently infects neurons, allowing its spread into the CNS via axonal transport. In addition, infection of immature dendritic cells has been associated with severe CNS disease, supporting a potential role of hematogenous dissemination in neuroinvasion. Overall, understanding the molecular mechanism and the role of host factors in NiV neuropathogenesis is crucial for developing effective strategies to combat NVD. The present review delves into the neuropathogenic mechanism and immunobiology of NiV infection, as well as advancements in therapeutic modalities and vaccines against NVD. Full article

Background: SARS-CoV-2 in sewage and aquatic environments may contribute to environmental dissemination of the virus. This study investigated the presence of SARS-CoV-2 RNA in sewage, sludge, and selected surface water sources in Dhaka, Bangladesh, and assessed related physicochemical parameters. Methods: Samples were collected from sewage pumping stations, one sewage treatment plant (STP), and selected rivers and ponds between September 2020 and January 2021. SARS-CoV-2 RNA was detected by RT-qPCR following nucleic acid extraction using a commercial kit. Temperature, pH, total dissolved solids (TDS), and dissolved oxygen (DO) were measured using portable instruments and conductivity was calculated from the TDS value. Results: SARS-CoV-2 RNA was detected in 57.1% of sewage samples and 53.3% of sludge samples. No viral RNA was detected in treated effluent from the STP, river, or pond, samples. River water showed little variation in physicochemical parameters, whereas pond and sewage samples exhibited differences in pH, conductivity, TDS, and DO. Conclusion: The presence of SARS-CoV-2 RNA in untreated sewage and sludge, but not in treated effluent, indicates that SARS-CoV-2 RNA was undetectable in the treated effluent. Further studies are needed to better understand the environmental persistence of SARS-CoV-2 in aquatic systems in Bangladesh. Full article

The persistent global threat posed by emerging and re-emerging RNA viruses, including SARS-CoV-2, influenza A(H1N1)pdm09, DENV-2, and CHIKV, highlights the critical need for novel and broad-spectrum antiviral agents. Building upon the established antiviral activity of the quinoline scaffold, this study employed a molecular hybridization strategy to design and synthesize a novel series of 1,2,3-triazole–quinoline derivatives (compounds 4a–4h). This approach strategically fused the bioactive quinoline nucleus with the pharmaceutically favorable 1,2,3-triazole ring. The new compounds were synthesized efficiently in three steps with moderate-to-high yields, and their structures were subsequently determined. Their inhibitory capacities against the four viruses and cytotoxicity across relevant cell lines were evaluated in vitro. The initial screening demonstrated that compounds 4a–4h possessed broad-spectrum antiviral activity, showing high inhibition percentages at 10 µM against SARS-CoV-2, DENV-2, and CHIKV. Notably, compounds 4c and 4e, substituted with methoxy and ethyl groups, respectively, displayed exceptional potency and safety against SARS-CoV-2, yielding high selectivity indices (SI: 1896.5 and 1265.8, respectively). Furthermore, in silico absorption, distribution, metabolism, and excretion (ADME) and molecular docking calculations suggested favorable drug-likeness profiles, including improved lipophilicity and non-P-glycoprotein substrate feasibility. The findings validate the molecular hybridization strategy, establishing this new class of compounds as promising, multi-target antiviral prototypes for further preclinical exploration against prevalent viral pathogens. Full article

Chronic hepatitis C virus (HCV) infection is an established risk factor for B-cell lymphoproliferative disorders and represents a paradigmatic model of infection-driven lymphomagenesis. Although direct-acting antivirals have markedly reduced the burden of HCV-related disease, HCV-associated lymphomas continue to occur. Moreover, HCV screening remains incomplete in some geographical areas and healthcare settings, leaving a substantial proportion of infected individuals unaware of their status. This narrative review integrates current evidence on the mechanisms linking chronic HCV infection to mixed cryoglobulinemia and overt B-cell non-Hodgkin lymphoma. HCV lymphotropism and persistent antigenic stimulation could initially promote the selection and expansion of autoreactive B-cell clones, while mixed cryoglobulinemia represents the most informative pre-lymphomatous risk condition. Cytokine-mediated survival signals, particularly those involving B-cell activating factor, reinforce clonal persistence and cooperate with host genetic susceptibility, impaired apoptotic control, and activation-induced cytidine deaminase-mediated genomic instability. The progressive acquisition of somatic driver mutations, copy-number alterations, and epigenetic and transcriptomic changes may enable selected clones to escape functional anergy and become increasingly independent of the original viral stimulus that, in turn, represents an initial trigger of the lymphoproliferative process. Recurrent abnormalities converge on NF-κB, NOTCH, chromatin-regulatory, apoptotic, and cell-cycle pathways, although HCV-associated lymphomas remain molecularly heterogeneous. Emerging microRNA profiles further contribute to the molecular characterization of the transition from chronic infection and cryoglobulinemia to lymphoma. Despite the availability of highly effective antiviral therapies, HCV-associated lymphomagenesis remains clinically relevant and continues to provide an especially informative model for understanding how chronic viral infection can drive human cancer development. Full article

Hepatitis E virus (HEV) infection, once regarded as a self-limiting hepatic disease confined to endemic regions, is now recognized as a systemic condition with a broad spectrum of extrahepatic manifestations. Among these, neurological complications—including peripheral neuropathies such as Guillain–Barré syndrome and neuralgic amyotrophy, and central nervous system involvement such as meningitis, encephalitis, and meningoencephalitis—are the most clinically relevant. Meningoencephalitis, though less common, is the most severe and underdiagnosed neurological expression of HEV infection. This narrative review examines current evidence on HEV-associated meningoencephalitis, covering epidemiology, pathogenesis, clinical features, and therapeutic strategies. Neurological disease is dominated by genotype 3 and frequently anicteric, with symptoms preceding or masking hepatic involvement. Pathogenesis is multifactorial, combining direct viral neurotropism—supported by HEV RNA detection in cerebrospinal fluid and replication in induced pluripotent stem cell (iPSC)-derived neurons and brain organoids—with immune-mediated mechanisms such as molecular mimicry and microglia-driven neuroinflammation. Diagnosis is often delayed by the absence of jaundice and low clinical suspicion, even though HEV remains an unrecognized cause in many unexplained encephalitis cases in high-income settings. Ribavirin remains the antiviral mainstay, but viral persistence within CNS sanctuary sites raises concerns about treatment adequacy and relapse; emerging antiviral and immunomodulatory strategies remain under investigation. HEV should be systematically considered in the diagnostic workup of unexplained neurological syndromes, regardless of overt hepatitis; heightened clinical awareness remains the most immediately actionable step toward reducing the burden of this still under-recognized condition. Full article

The largemouth bass (Micropterus salmoides) is persistently threatened by Micropterus salmoides rhabdovirus (MSRV) and largemouth bass ranavirus (LMBV), highlighting the need for combined immunization strategies. Here, a bivalent DNA vaccine pEGFP-G-MCP was constructed by concatenating the highly immunogenic fragments of MSRV glycoprotein (MSRV-G) and LMBV main capsid protein (LMBV-MCP) using a flexible linker peptide, and its immunogenicity and protective effect were systematically evaluated. Fish were immunized by intramuscular injection of 200 ng of plasmid on day 1, followed by a booster immunization on day 8. Blood and tissues were collected at 10, 20, and 30 d post-last immunization. The results showed that pEGFP-G-MCP immunization induced G- and MCP-specific antibodies and upregulated the expression of immunity-related genes. The bivalent vaccine achieved a relative percent survival (RPS) of 93.3% against MSRV and 90.0% against LMBV, which were higher than those of the monovalent vaccine groups. Additionally, the bivalent vaccine reduced viral mRNA and alleviated pathological damage in MSRV- or LMBV-infected fish. These results indicate that pEGFP-G-MCP confers immune protection against MSRV and LMBV, providing a foundation for combined prevention and control of MSRV and LMBV. Full article

Equine sarcoid is the most common cutaneous neoplasm of equids and represents a distinctive model of virus-associated tumor persistence. Although bovine papillomaviruses, particularly BPV-1 and BPV-2, are recognized as the main etiological agents, viral infection alone does not fully explain the clinical heterogeneity, frequent recurrence, and limited spontaneous regression of these lesions. This review summarizes current evidence on the molecular and cellular mechanisms underlying equine sarcoid pathogenesis, with emphasis on the interaction between BPV infection, host signaling pathways, tumor microenvironment dynamics, and multi-omic evidence of host regulatory networks. BPV oncoproteins, especially E5, promote fibroblast transformation through PDGFβR activation, downstream PI3K/AKT, MAPK and p38 signaling, altered cell survival, and immune evasion mediated by impaired antigen presentation. However, sarcoid persistence appears to depend on broader host-driven processes, including extracellular matrix remodeling, activated fibroblastic and myofibroblastic phenotypes, chronic inflammatory signaling, and ineffective immune clearance. Recent transcriptomic and epigenomic studies further indicate that long non-coding RNAs, DNA methylation changes, circulating microRNAs, and recently identified virus–host chimeric transcripts may contribute to stabilization of the neoplastic phenotype and may represent future biomarkers. Overall, this review proposes a virus-initiated, host-sustained conceptual framework for equine sarcoid pathogenesis, in which viral oncogene activity and host tissue reprogramming cooperate to promote lesion persistence, recurrence, and therapeutic resistance. Full article

Background/Objectives: Bovine respiratory disease (BRD) remains a major concern in cattle research, and the long-term effects of vaccination on health and immune responses are not well defined. This study compared gene expression in vaccinated (VAX) and unvaccinated (NOVAX) preweaned calves and subsequent BRD development during backgrounding. Methods: Whole blood was collected at four timepoints (TIME; T1-4; median age 107, 114, 183, and 230, respectively) from 73 bull calves enrolled in a blinded randomized controlled trial; VAX calves received a commercial attenuated multivalent viral vaccine at T1 and T3. Results: Whole-blood transcriptomics was used to quantify mRNA, identifying 5364 differentially expressed genes (DEGs) for TIME, 84 DEGs for vaccination (VAX), and 129 for BRD status using both glmmSeq and QLF testing (glmmSeq only DEGs: 11,068 TIME, 358 VAX, and 9241 BRD). VAX calves at T3 were clustered uniquely with the enrichment of pathways related to the cellular response to stress, neutrophil degranulation, and antigen processing and presentation compared to NOVAX cattle and VAX at other timepoints. Interferon pathways, natural killer cell responses, and neutrophil activity were generally absent across all timepoints, while antigen presentation pathways were persistently enriched. Regardless of vaccination or future BRD diagnosis, immunological development over time was indicated by DEGs related to adaptive immunity, lymphocyte development, and inflammatory resolution. At T4, cattle diagnosed with BRD during backgrounding had differential gene expression related to oxygen transport, hemoglobin function, and metabolic processes compared to cattle that remained healthy. Conclusions: This study provides insights into the possible genomic mechanisms underlying vaccine responses and preclinical BRD susceptibility in preweaned beef cattle. Full article

Diarrhea and impaired intestinal development are major constraints in newly hatched domestic pigeons raised for meat production, leading to reduced growth performance and increased reliance on antimicrobial interventions. Cecropin AD (CAD) is a broad-spectrum antimicrobial peptide with potential activity against bacterial pathogens and may represent an alternative strategy for improving intestinal health in poultry. In this study, we evaluated the safety and biological effects of a recombinant Newcastle disease virus (NDV) expressing CAD (rTS-CAD₃) in one-day-old domestic pigeons. Pigeons were inoculated with rTS-CAD₃, parental TS09-C, or PBS and monitored for growth performance, diarrhea incidence, viral RNA persistence, inflammatory responses, intestinal bacterial abundance, gut microbiota composition, intestinal morphology, and epithelial barrier function. rTS-CAD₃ caused no mortality, detected only transient viral RNA, and did not induce excessive inflammatory responses. Compared with TS09-C and PBS controls, rTS-CAD₃ significantly increased body weight gain and average daily gain while reducing diarrhea incidence. Importantly, rTS-CAD₃ decreased intestinal Escherichia coli abundance, reshaped the gut microbiota by reducing Proteobacteria and Escherichia–Shigella while increasing Firmicutes and Lactobacillus, improved villus height and the villus-to-crypt ratio, and enhanced occludin expression. These findings demonstrate that NDV-vectored CAD delivery can reduce intestinal bacterial burden, increase occludin expression, and alleviate diarrhea in domestic pigeons. The rTS-CAD₃ represents a promising antimicrobial peptide-based strategy for reducing spontaneous diarrhea and dependence on conventional antibiotics in poultry production. Full article

Gut-associated lymph nodes (GALNs) constitute an important anatomical reservoir during early and chronic human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection, but the fate of this compartment during terminal AIDS remains unclear. This study investigated viral persistence and lymph node injury in a rhesus macaque with long-term SIVmac239 infection and end-stage AIDS, characterized by profound CD4+ T cell depletion (30 cells/μL) and persistent viremia (1192 copies/mL). At necropsy, GALNs, including mesenteric, paracolic, and ileocecal lymph nodes, and non-gut-associated lymph nodes (NGALNs), including hepatic hilar, common iliac, and inguinal lymph nodes, were collected for viral RNA/DNA quantification, histopathology, immunofluorescence, and transcriptomics. SIV DNA was markedly lower in GALNs than in NGALNs, whereas SIV RNA was detectable only in NGALNs. GALNs exhibited extensive fibrotic remodeling, paracortical collapse, severe CD4+ T cell loss across B cell and paracortical regions, and pronounced CD8+ T cell accumulation within B cell zones. Transcriptomic profiling further revealed an exhaustion signature in GALNs, with reduced DNA replication and repair, impaired cell-cycle activity, and suppressed RNA processing, accompanied by activation of innate immune programs and attenuation of adaptive immune responses. These findings indicate that, during terminal AIDS, GALNs no longer serve as the predominant viral reservoir but instead undergo preferential and severe structural and functional exhaustion. This case highlights marked anatomical heterogeneity in lymph node vulnerability during advanced disease and supports a model in which collapse of the gut-associated immune barrier contributes to disease progression toward terminal AIDS. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes an immune-mediated neurological syndrome, which persists long after infection. Mechanisms for SARS-CoV-2-associated neurological complications are multifactorial, with an increased risk of drug abuse such as methamphetamine (meth). SARS-CoV-2 infection and its viral proteins play pivotal roles in coronavirus disease 2019 (COVID-19)-associated neuroinflammation, which can lead to long COVID. We hypothesize that meth augments activation of the microglial NOD-, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome by the SARS-CoV-2 nucleocapsid (N) protein, resulting in neuroinflammation. To test this hypothesis, we investigated the effect of N-protein and meth on NLRP3 inflammasome activation in primary rat microglial cultures using enzyme-linked immunosorbent assay (ELISA), Reverse Transcription quantitative Polymerase Chain reaction (RT-qPCR), western blot (WB), and immunofluorescence assay (IFA). Our results showed that meth augmented N-protein-induced microglial activation, as evidenced by increased ionized calcium-binding adapter 1 (Iba-1) expression. The addition of meth to the microglial cultures treated with N-protein increased proinflammatory cytokine production. Meth augmentation of N-protein-induced neuroinflammation was further supported by increased inducible nitric oxide synthase (iNOS)-mediated nitric oxide (NO) production. The effects of meth on N-protein-associated inflammatory responses were significantly attenuated by MCC950, a specific NLRP3 inhibitor. Moreover, meth-associated NLRP3 activation was either blocked by the opioid sigma1-receptor (σ1_-R) inhibitor BD1047 or by σ1R siRNA knockdown. Taken together, these results demonstrated that meth augmented SARS-CoV-2 N-protein-induced neuroinflammation via microglial σ1_-R and the NLRP3 inflammasome, which may underlie the pathogenesis of neurological manifestations in COVID-19, such as long COVID with meth abuse. These results may also underscore the impact of drug abuse on long COVID and provide targets for the development of therapeutic strategies to control the neurological outcomes of long COVID. Full article

Background: The RNA interference (RNAi) pathway is a highly conserved antiviral mechanism in eukaryotes, including insects such as fruit flies. Many viruses have therefore evolved mechanisms that protect their transcripts and/or genomes; how effectively RNAi can act is thus a question that must be answered case-by-case. Methods: We demonstrate that the RNAi machinery can successfully combat Drosophila A virus (DAV) in persistently infected Drosophila melanogaster S2 cell lines, but only when supported with exogenous triggers. Since such an infection poses a challenge to the fitness of cells and the reproducibility of results obtained with them, our approach provides a convenient method to recover precious experimentally modified cell lines from infection through the application of exogenous double-stranded RNA (dsRNA) targeting the DAV sequence. The in vitro transcribed dsRNAs were applied to infected S2 cells via direct “soaking,” utilizing the cells’ natural endocytic uptake. Results: We monitored treatment efficacy via RT-PCR-based detection of viral sequences, and our results demonstrate that continued application of DAV-specific dsRNAs led to a reduction in viral abundance and all eight tested cell lines appeared DAV-negative within several weeks of treatment. While a set of cell lines exhibited viral recurrence several weeks after the cessation of treatment, others remained virus-free for at least 16 weeks, suggesting that a permanent “cure” can indeed be achieved. Notably, while RNAi activation effectively cleared DAV in some cell lines, no beneficial effect was observed for a concomitantly applied Drosophila X-virus (DXV) treatment in the co-infected cultures. Conclusions: This suggests that DXV has more efficient evasion mechanisms but cannot protect DAV in trans. Our protocol thus provides a robust, scalable approach for clearing persistent DAV infections, but may not be effective against all viruses known to infect Drosophila cell cultures. Full article

Residual inflammation remains a hallmark of treated HIV infection despite durable viral suppression. Whether previous SARS-CoV-2 infection is associated with residual inflammation in people living with HIV (PLWH) remains incompletely understood. This study evaluated the association between previous COVID-19 and persistent inflammation in virally suppressed PLWH. In this retrospective observational single-center study, 286 adults receiving antiretroviral therapy between January 2023 and December 2025 were included. Patients were stratified according to documented SARS-CoV-2 infection history. A secondary analysis included 231 individuals with sustained viral suppression (HIV-RNA < 50 copies/mL). Inflammatory biomarkers, immune recovery parameters, metabolic characteristics, and independent predictors of elevated inflammatory biomarker levels were evaluated. Previous SARS-CoV-2 infection was associated with significantly higher concentrations of C-reactive protein, interleukin-6, tumor necrosis factor-α, erythrocyte sedimentation rate, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio (all p < 0.01). Among virally suppressed patients, elevated inflammatory biomarker levels were associated with lower CD4+ T-cell counts, lower CD4/CD8 ratios, obesity, metabolic syndrome, dyslipidemia, and hepatic steatosis. Previous SARS-CoV-2 infection, obesity, metabolic syndrome, and CD4+ T-cell counts < 500 cells/mm³ were independently associated with elevated inflammatory biomarker levels. Previous SARS-CoV-2 infection was independently associated with an unfavorable inflammatory profile in virally suppressed people living with HIV. Given the retrospective observational design, these findings should be interpreted as associations rather than evidence of causality. These findings suggest that long-term host-related and metabolic factors may contribute to residual inflammation beyond viral control and highlight the need for prospective studies investigating strategies to reduce residual immune activation in treated HIV infection. Full article

HIV-associated neurocognitive disorders (HAND) persist despite effective antiretroviral therapy, indicating that chronic neuroimmune dysfunction extends beyond active viral replication. Among HIV-1-derived factors, the viral proteins Tat and gp120 are contributors to sustained brain inflammation. Nevertheless, their comparative impact in genetically vulnerable neural environments remains unclear. Here, we performed a secondary transcriptomic analysis of publicly available RNA-seq data derived from the striatal tissue of hSNCA^A53T Gba1^+/L444P mice, a model combining α-synuclein overexpression with Gba1-associated lysosomal impairment, following unilateral intrastriatal injection of Tat or gp120. Both proteins induced robust transcriptional remodelling selectively in the injected striatum. Tat primarily elicited a broad inflammatory amplification programme encompassing innate immune sensing, chemokine recruitment, adaptive immune engagement, and loss of homeostatic support. gp120 preferentially activated antigen presentation, complement, oxidative stress, and lysosomal–phagocytic effector pathways consistent with immune-mediated synaptic stress. Despite these distinct profiles, Tat and gp120 converged on a shared microglia-centred effector core. Contralateral striatal tissue was analyzed as distal non-injected tissue to explore the spatial distribution of transcriptional responses and minimal and protein-specific effects were reported. These findings provide a mechanistic framework for HAND heterogeneity and suggest that HIV protein-driven neuroimmune transcriptional programmes may create a molecular environment compatible with increased neurodegenerative vulnerability in lysosome-compromised, α-synuclein-sensitized brains. Full article