Virology Journal最新文献

Background: Microvascular damage by oxidative stress is central in the pathogenesis of generalized COVID-19 disease. Hence, a disbalance of endothelial-derived oxidative and anti-oxidative factors in COVID-19 patients can be expected, and the extent of this disbalance might correlate with disease severity.

Methods: We measured xanthine oxidase (XO), superoxide dismutase (SOD), catalase (CAT), and ischemia modified albumin (IMA) in serum samples of 166 COVID-19 patients and 238 controls. We then cathegorized the COVID-19 group further into mild, moderate, severe and lethal courses and tested these for correlation with each parameter alone, and with multi-parametric logistic regression analysis.

Results: Compared to controls, XO was significantly lower in COVID-19 patients, SOD and CAT were significantly higher. Difference in IMA was insignificant. In the single parameter analysis, only CAT concentration was significantly correlated to disease severity. In the logistic regression analysis, XO and SOD were negatively correlated with disease severity.

Conclusions: Oxidative stress in COVID-19 does derive from other sources than endothelial XO. The rise in protective enzymes like SOD and CAT may be the result of enzyme induction. Since the correlation of CAT with disease severity was highest, we propose this parameter as a possible predictor for a severe clinical course.

Infectious bursal disease (IBD) is an important viral disease that causing severe immunosuppression in young chickens. This current study compared the pathogenicity of very virulent IBDV (vvIBDV) and Chinese novel variant IBDV (nVarIBDV) strains in Specific Pathogen-Free (SPF) chickens. Chickens infected with the nVarIBDV strain exhibited no clinical signs or mortality, with mild edema and swelling in bursas during early infection, followed by progressive atrophy by the seventh- and fifteenth-days post-infection (dpi). In contrast, vvIBDV displayed severe systemic disease, with early onset ruffled feathers, hemorrhages on the thigh muscles. While both strains caused bursal atrophy, the vvIBDV strain induced more severe systemic pathology, characterized by hemorrhages in bursa, renal and hepatic degeneration, with 50% mortality. The vvIBDV induced severe reduction in Bursa-to-Body Weight (B/BW) ratio, reaching 1.042 ± 0.302, indicating significant immunosuppressive effect. While, the nVarIBDV-infected group showed marked reduction in the B/BW ratio to 1.269 ± 0.269, showing 70% decrease compared to the control group. The results of histopathology showed a mild bursitis, lymphoid depletion, and interfollicular connective tissue proliferation in the nVarIBDV-infected chickens. While, vvIBDV-infected chickens induced a severe bursitis with necrosis of lymphoid follicles and interfollicular fibrous tissue proliferation indicating lymphoid depletion. Moreover, the challenge with nVarIBDV and vvIBDV alter the immune response of a trivalent inactivated vaccine either before vaccination or after vaccination. This study provides valuable data about the pathogenicity of two cocirculating IBDVs in Egypt and highlighted the need for strict routine monitoring for nVarIBDV infection in chicken flocks as it has no clinical signs. Further research may be required to assess the efficacy of the currently available IBD vaccines in Egypt against these strains.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a major global health burden in terms of acute infection and long-term consequences. Approximately 10% of infected experience autonomic dysfunction, cardiovascular complications, and neurological impairments. While immune dysregulation, persistent viral reservoirs, chronic inflammation, gut dysbiosis, and vascular dysfunction are implicated, the exact pathophysiological mechanisms of Long COVID remain unclear. Additionally, treatment options are limited and challenging to prescribe due to symptom heterogeneity. Non-pharmacological interventions such as increased salt intake, elimination diets for gastrointestinal symptoms, and cognitive pacing for fatigue may not be sufficient for severe symptoms. Moreover, pharmacological interventions such as β-blockers, calcium channel blockers, pyridostigmine, antihistamines, and low-dose naltrexone can improve tachycardia, fatigue, and brain fog but there are no standardized guidelines. In light of evidence supporting a strong association of Long COVID with gut dysbiosis, probiotics have emerged as a promising intervention. Clinical studies have shown that Bacillus coagulans, Bacillus subtilis, Lactobacillus acidophilus, and Bifidobacterium species can improve fatigue, gastrointestinal health, and overall physical and mental well-being in Long COVID patients. Large-scale randomized controlled trials are warranted to validate probiotic efficacy in Long COVID and reduce burden on individual health and healthcare institutions.

Potato crops in Bangladesh are significantly threatened by viral diseases, underscoring the need for comprehensive virome profiling to inform sustainable management strategies. In this study, we employed high-throughput sequencing (HTS) to characterize the viral diversity in symptomatic potato leaves collected from five major potato-growing districts. A total of 10 distinct viruses were identified, representing six families and nine genera. Among these viruses, potato virus X (PVX) was the most abundant, followed by potato virus Y (PVY) and potato virus S (PVS). Notably, potato virus V (PVV) was detected for the first time in Bangladesh and, to our knowledge, not previously reported in South Asia. Additionally, we assembled the complete genome sequence of a potato virus A (PVA) isolate from Bangladesh, which was highly similar to previously reported PVA genomes. Phylogenetic analysis revealed that the Bangladeshi PVA and PVV isolates share close evolutionary relationships with global strains, particularly those from Europe and the Americas, suggesting historical or trade-related linkages. Co-infection analysis showed a high frequency of mixed infections, with PVY, PVS, and potato leafroll virus (PLRV) being the most common combinations. The correlation analysis identified strong statistical associations among specific viruses [e.g., between potato aucuba mosaic virus (PAMV) and tomato leaf curl New Delhi virus (ToLCNDV)], indicating frequent co-occurrence patterns that warrant further investigation; however, causal mechanisms were not inferred from these data. Geospatial analysis revealed that Dinajpur and Panchagarh districts had the highest overall viral prevalence, while Thakurgaon exhibited the lowest diversity of infections. These findings highlight the complexity of the potato virome in Bangladesh, emphasizing the threat posed by the dominance of PVY and the emergence of novel viruses like PVV. This study provides a foundational framework for future research on potato virus epidemiology and paves the way for sustainable agricultural practices to mitigate the impact of viral infections on potato production in Bangladesh.

Introduction: Enterovirus A71 (EV71)-associated encephalitis lacks targeted neuroprotective therapy. Experimental data implicate endoplasmic reticulum (ER) stress and ferroptosis in neuronal injury. We tested whether the chemical chaperone 4-phenylbutyric acid (4-PBA) mitigates EV71 neuropathology by interrupting the ER-stress-ferroptosis axis.

Materials and methods: Neonatal mice were infected with EV71 and treated with 4-PBA; survival, body weight, and neurological scores were recorded. Brain injury was assessed by histology (H&E, Nissl, TUNEL) and inflammatory cytokines. ER-stress markers (GRP78, CHOP), ferroptosis indices (GPX4, Fe²⁺, reactive oxygen species, malondialdehyde, superoxide dismutase, glutathione), and viral burden (VP1 mRNA) were quantified. Complementary experiments in EV71-infected HT22 neuronal cells evaluated 4-PBA with or without erastin to probe ferroptosis involvement.

Results: 4-PBA improved survival and clinical scores, attenuated neuronal loss, and reduced brain inflammation. Treatment suppressed ER-stress markers, restored GPX4 and antioxidant defences, and lowered Fe²⁺, reactive oxygen species, and malondialdehyde. VP1 mRNA decreased in brain tissue. In HT22 cells, 4-PBA reduced cytotoxicity and lipid-ROS accumulation; erastin abrogated these benefits, supporting a ferroptosis-dependent mechanism.

Conclusions: These data identify an ER-stress-ferroptosis pathway as a driver of EV71 neurotoxicity and demonstrate that repurposed 4-PBA interrupts this cascade to confer functional neuroprotection in vivo and in neuronal cells. To our knowledge, this provides the first in vivo evidence that pharmacologic relief of ER stress can inhibit ferroptosis to ameliorate EV71 encephalitis, highlighting a translational strategy for neurotropic viral disease.

Background: Orthohantaviruses are zoonotic RNA viruses that cause hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. Their slow replication, lack of cytopathic effects, and variable biosafety requirements have long hindered the standardization of infection assays and antiviral testing. While serological and pseudotype-based systems enable high-throughput screening, scalable assays that directly quantify full-cycle Orthohantavirus infection remain limited.

Results: Here, we present a modular BSL-2 workflow that integrates standardized virus stock generation with complementary infection-quantification readouts. The platform combines (i) titration-guided pooling of daily supernatants to produce high-titer virus stocks without ultracentrifugation, (ii) a cross-reactive monoclonal antibody recognizing conserved nucleocapsid epitopes across multiple Orthohantavirus species, and (iii) three quantitative detection methods: qPCR, in-cell ELISA, and intracellular flow cytometry. Flow cytometry was used as the primary readout because it enables rapid, quantitative, single-cell detection of infection and can be readily integrated with multiparametric analyses. Using this system, we quantified the antiviral effects of rottlerin and observed distinct dose‒response profiles among Puumala, Tula, and Prospect Hill viruses.

Conclusion: Our workflow delivers a practical, reproducible, and scalable toolkit for comparative Orthohantavirus studies, enabling quantitative infection analysis and small-molecule testing under standard laboratory conditions.

Rift Valley fever (RVF) is a mosquito-borne zoonosis of major concern for human and animal health, yet no licensed human vaccine exists. Here, we engineered a self-assembling nanoparticle vaccine candidate by genetically fusing the RVF virus glycoprotein Gn to the N-terminus of a hybrid bacterial ferritin, generating nanoparticles that display 24 copies of Gn on their surface. Cryo-electron microscopy at 6 Å resolution confirmed ordered and symmetric presentation of the antigens, consistent with the structural models of ferritin and Gn. When incubated with human monocyte-derived dendritic cells, the Gn-ferritin nanoparticles were efficiently internalized and induced robust expression of maturation markers (e.g., CD54, CD83, CD86) and secretion of pro-inflammatory cytokines (e.g., IL-1β, IL-6, IL-12p40, TNF-α), in contrast to soluble Gn or ferritin controls. These findings demonstrate that ferritin nanoparticles provide a structurally defined and immunologically active platform for RVF virus antigen display, establishing a foundation for the development of safe and effective subunit vaccines against this emerging pathogen.

Influenza A virus (IAV) infections play a substantial role in human disease, hospitalization, and economic loss. In an effort to better understand the intracellular effects that IAV replication has on individual host cells, this study set out to analyze an existing single-cell RNA sequencing (scRNAseq) dataset to identify the different metabolic pathways disrupted in cells infected with IAV. Specifically, these analyses consisted of calculating differential expression, signaling pathway enrichment, and text mining methods on a publicly available dataset consisting of 2041 mammalian MDCK cells infected with H9N2 IAV to model cross-species spread of endemic avian influenza. Interestingly, this dataset detected cells that were infected by viruses that carried less than a full set of genome segments, allowing us to ascribe impacts on host gene expression to specific viral genes. The results from this analysis enabled us to observe (1) the differences in host cellular gene expression caused by individual IAV segments, (2) the effects of various segment combinations on the host response, and (3) the segment-specific disruptions in signaling pathways related to three categories: virus replication, host immune response, and cell cycle. Deeper examination of these trends will improve our understanding of the mechanistic effects of responses caused by IAV at the molecular level and improve the ongoing development of host-based anti-viral therapeutics.

Dengue is a frequent mosquito borne infection with no antiviral medications approved and drug repurposing is an economical and time-saving method of creating an efficient therapy. This research has chosen RNA-dependent RNA polymerase (RdRp) of non-structural protein 5 (NS5) of dengue virus serotype 2 (DENV-2) as a therapeutic. PyRx software was used to perform virtual screening of FDA-approved drugs available in the ZINC database based on their structure. Out of the top15, doxorubicin and rifamycin were selected as candidate drugs to undergo molecular docking and molecular dynamics (MD) studies. Docking showed binding energies of - 8.9 kcal/mol for doxorubicin and - 8.6 kcal/mol for rifamycin. Simulations of MD confirmed that interactions of doxorubicin with the palm domain of RdRp occur in a stable way, which may result in the inability to promote viral replication. In Vero cells, cytotoxicity tests showed that concentrations below 12.25 µg/mL of doxorubicin were not toxic, whereas higher concentrations had morphological effects with a CC₅₀ of approximately 150 µg/mL. MTT-based cell viability assays in DENV-2-infected Vero cells showed dose-dependent effects on cell viability, with an IC₅₀ of 86.52 µg/mL. Conclusively, doxorubicin exhibited indirect, cell viability-based effects in DENV-2-infected Vero cells at non-cytotoxic concentrations, however, a low selectivity index (SI ≈ 1.7) and cytotoxicity highlights a narrow therapeutic window, limiting its potential for direct clinical use. The development of safer derivatives, optimized dosing and targeted delivery systems, e.g., nanocarriers should be considered in future research to improve efficacy and decrease toxicity.