Virology Journal最新文献

Purpose: This study aimed to evaluate the diagnostic value of red blood cell distribution width-to-albumin ratio (RAR), a biomarker integrating hematological and metabolic information, for COVID-19 pneumonia.

Methods: This retrospective study analyzed clinical data from 2,205 patients with COVID-19. RAR values were calculated as the ratio of red blood cell distribution width (RDW) to serum albumin concentration. Diagnostic performance of RAR in COVID-19 pneumonia was assessed using receiver operating characteristic (ROC) curve analysis, and the optimal cut-off was determined. Mediation analysis was conducted to examine the role of chronological age in the association between RAR and COVID-19 pneumonia risk.

Results: Among COVID-19 patients, RAR demonstrated strong diagnostic performance for COVID-19 pneumonia, with area under the curve (AUC) of 0.769 [95% confidence interval (CI): 0.747-0.791], sensitivity of 76.8%, and specificity of 65.3% at the optimal cut-off value of 0.154. Its diagnostic utility likely stems from simultaneously reflecting hematopoietic dysfunction (elevated RDW) and systemic metabolic imbalance (hypoalbuminemia). Mediation analysis indicated that chronological age accounted for 14.16% of the association between elevated RAR and COVID-19 pneumonia risk (β = 0.1139, 95%CI: 0.0802-0.1524).

Conclusion: RAR represents a promising biomarker for the early detection and risk stratification of COVID-19 pneumonia. By simultaneously capturing hematologic and metabolic disturbances, RAR provides a more comprehensive reflection of disease severity. The observed age-mediation effect suggests that elderly individuals with elevated RAR may face heightened risk, warranting enhanced clinical monitoring or prioritized intervention.

Rubus species, including raspberry and blackberry, are affected by over 40 known viruses that can impact fruit yield, plant vigor, and germplasm movement. These species differ markedly in their response to viral infection, yet the factors that contribute to susceptibility are unknown. We hypothesize this is due to differences in virus accumulation dynamics. We utilized an infectious clone of blackberry chlorotic ringspot virus to assess replication efficiency in 'Munger' black raspberry (Rubus occidentalis, L.), a virus indicator for Rubus viruses, and 'Natchez' blackberry (Rubus L. subgenus Rubus Watson), a cultivar that typically is asymptomatic to single virus infections. This study demonstrated that virus accumulation in 'Munger' is over 4.4 × 10⁵-fold higher than in 'Natchez,' based on a model-derived estimate averaged across sampling time points, providing evidence that the host genotype plays a key role in supporting virus replication. These findings deepen our understanding of virus-host interactions and further validate the use of 'Munger' as a virus indicator for Rubus.

Rotaviruses A (RVA) are the most common cause of diarrhea-related death in children under the age of five. Because RV vaccines are live attenuated, their use is limited. This work aimed to develop a multi-epitope vaccination against RVA using reverse vaccinology approaches. The viral protein 6 (VP6) was targeted for predicting B-cell and T-cell epitopes, and the best epitopes from its conserved regions were linked by appropriate linkers; additionally, 50 S ribosomal protein L7/L12 was inserted as an adjuvant to the vaccine's N-terminus. The designed vaccine revealed satisfactory antigenicity, allergenicity, toxicity, and physicochemical characteristics. The molecular docking and molecular dynamics (MD) simulation showed strong binding interactions between the vaccine and toll-like receptor 4 (TLR4), signifying improved antigen presentation efficacy. The vaccine immunity simulation showed a significant rise in immunoglobulins and cytokines. Furthermore, the vaccine candidate showed a high likelihood of successful expression in Escherichia coli (E. coli). Our findings suggest that the multi-epitope vaccine candidate exhibits significant potential; however, experimental evaluations are necessary to determine its ability to stimulate the immune system.

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB) continues to pose significant public health in clinical settings due to its remarkable genomic plasticity and resistance to available therapeutic drugs, including carbapenems. Bacteriophage has emerged as an optimistic solution capable of addressing such drug resistance dilemma. This study represents a comprehensive characterization of a novel Acinetobacter phage with potential application against CRAB-associated wound infections.

Methods: Sewage sample was obtained, processed, and enriched with A. baumannii M13 phage(s) for the purpose of phages' isolation. The isolated phage was examined using transmission electron microscope (TEM) and identified in terms of host range and efficiency of plating through spot test and plaque assay, respectively. Phage stability was screened following thermal, pH and ethanol assays. Replication kinetics were investigated through adsorption and single step growth curve. Furthermore, the in-vitro antibacterial potential was verified through measuring the optical density of the treated M13 culture at different Multiplicity of infections (MOIs) over 6 h shaking incubation. This is in tandem with preliminary screening of the vB_AbaM_MU1 safety through genomic and phylogenetic analysis of the isolated phage.

Results: A novel lytic Acinetobacter phage vB_AbaM_MU1 was isolated and categorized as T4-like Myovirus with genomic size 167.200 bp, which was classified into the family Straboviridae in class Caudoviricetes, based on morphological and genomic analyses. It showed lytic efficiency against 9/17 CRAB strains. Infectivity and structural integrity revealed thermal stability up to 60℃, pH tolerance within pH range (3-11), sensitivity to different EtOH concentrations (10%, 50%, 75%, and 95%). In addition, vB_AbaM_MU1 displayed distinctive infection kinetics with 6 min adsorption, short latent (over 30 min), and high bursting (326 PFU/infected cell). The in-vitro bacteriolytic infectivity revealed robust and steady antibacterial action at MOI of 1 and above.

Conclusion: These findings provide a strong, well-justified foundation for considering vB_AbaM_MU1 phage as successful candidate for phage therapy in treating CRAB- induced wound infections.

Background: Hendra virus (HeV) is a bat-adapted zoonotic henipavirus belonging to the Paramyxoviridae family. It is classified as a biosafety level 4 (BSL-4) pathogen owing to its broad host range and high fatality rate. Currently, no vaccines or therapeutics are approved for human use. Viral entry is mediated by the attachment (G) and fusion (F) glycoproteins; the heavily glycosylated G protein is responsible for receptor binding.

Methods: The extracellular domain of HeV-G was expressed in Expi293F cells and its glycosylation sites and glycan composition were identified by mass spectrometry. A series of functional assays-including viral entry, receptor binding, cell-cell membrane fusion, antibody neutralization and immunogenicity-were performed to delineate the role of each N-linked glycosylation site.

Results: Glycan profiling of HeV-G identified seven N-linked and multiple O-linked glycosylation sites, revealing that the stalk residues (N72, N159) predominantly carry high-mannose glycans, whereas the head-domain N-glycan sites (N306, N378, N417, N481, N529) are primarily modified with complex glycans. Notably, among the head-domain sites, N481 also harbors a substantial proportion of high-mannose glycans. Functional assays revealed that removal of N-glycans at N159, N306 and N417 markedly reduced membrane fusion. The N159 residue is a key site for fusion triggering, and its function is tolerant to specific amino acid substitutions, which may contribute to stabilizing or facilitating the conformational cascade required for F protein-mediated membrane fusion. The N529Q mutant specifically decreased EB3 binding by 2.6-fold, correlating with reduced infectivity. Binding assays with neutralizing antibodies showed that most N-glycan deletions had negligible effects, except that N159Q and N481Q reduced affinity to nAH1.3. Immunization studies in mice demonstrated that N-glycans had minimal impact on humoral immunity, with only minor site-specific differences.

Conclusion: These findings provide a comprehensive characterization of HeV-G glycosylation, reveal site-specific roles of N-glycans in viral entry, receptor binding and membrane fusion, and offer new insights for vaccine and antibody development.

Background: Dengue fever continues to exert significant global impact, affecting populations worldwide with considerable public health and economic consequences. There is no antiviral drug for dengue. This study focuses on hypericin, a naturally occurring compound from Hypericum perforatum L. whose anti-dengue properties have been underexplored. We systematically examined its antiviral efficacy against dengue virus (DENV), revealing strong inhibitory effects and clarifying its precise antiviral mechanism.

Methods: The study assessed the efficacy of hypericin against DENV using various scientific methods like plaque assays and Western blotting. We looked into its antiviral mechanism. We used a time-of-addition approach during our research. Moreover, the basic mechanisms involved were studied through molecular docking, surface plasmon resonance (SPR), and co-immunoprecipitation (Co-IP).

Results: This study demonstrated that hypericin exhibits broad-spectrum antiviral activity against DENV-2 in cell lines derived from multiple species. In time-of-addition experiments, it showed inhibitory effects under co-treatment, direct virucidal, and post-treatment conditions. Crucially, hypericin primarily blocked viral attachment and entry stages, thereby effectively reducing intracellular viral load. Mechanistic investigations revealed a interaction between hypericin and the E protein, evidenced by a computational docking score of -7.0 kcal/mol and an experimental SPR-derived Kd of 7.18 µM. Furthermore, Co-IP assays demonstrated that hypericin competitively blocks the association between the E protein and its cellular receptor, HSP70.

Conclusion: As per these findings, the E protein was seen to be a target of hypericin with an antiviral activity against DENV-2 at multiple stages by limiting viral adsorption and viral entry projecting a molecular basis for the candidate molecule as a possible anti-dengue agent.

Phage therapy is currently gaining attention as a promising alternative for treating multi-drug resistant (MDR) bacterial infections, including urinary tract infections (UTIs). However, most studies have reported bacterial regrowth in vitro after hours of co-incubation with phage-host bacteria. In this study, we evaluated whether using a phage alone or combined with gentamicin could delay or prevent bacterial regrowth in vitro, in human urine, and in a rat model. The previously characterized lytic phage vB_Eco_ZCEC08 was combined with gentamicin to target clinical Uropathogenic Escherichia coli (UPEC) infection. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of gentamicin against the resistant EC08 clinical isolate were determined, revealing high gentamicin resistance (MIC = MBC, 500 µg/mL). Time-killing assays demonstrated that combining ½ MIC gentamicin (250 µg/mL) with the phage at different multiplicities of infection (MOIs) effectively controlled bacterial growth and prevented regrowth, even after 72 h, in both in vitro culture media and urine. Notably, the phage's growth exhibited distinct dynamics when used alone versus in combination with gentamicin in both in vitro and in vivo experiments. The combination showed higher replication rates in both urine and the rate model. For the in vivo experiments, bacterial counts showed significant reductions with both phage therapy and combination therapy compared to gentamicin monotherapy. Histopathological analysis of the tissues treated with the combination presented better tissue integrity than either monotherapy. These findings support the potential of phage-antibiotic combinations as an effective strategy against MDR-UPEC infections, highlighting the need for further studies to optimize treatment regimens for clinical applications.

Background: Chronic hepatitis B (CHB) with positive HBeAg status constitutes a significant contributor to the development of liver cirrhosis and hepatocellular carcinoma. Pegylated interferon-alpha (pegIFNα) is a common treatment, but its response rate remains limited, and the underlying mechanisms are not fully understood.

Methods: Eighty-two HBeAg-positive CHB patients were enrolled. miR-194-5p expression, HBeAg, and HBV DNA levels were detected using qRT-PCR, ELISA, and quantitative PCR, respectively. ROC and logistic regression analyses were performed. Cellular experiments, including dual-luciferase reporter and rescue assays, along with Western blot analysis of JAK-STAT pathway proteins, were conducted to verify targeting and function.

Results: Complete response (CR) patients had significantly lower baseline HBV DNA than suboptimal response (SR) patients. After 48 weeks of pegIFNα therapy, miR-194-5p expression decreased notably in the CR group and correlated positively with HBV DNA and HBeAg levels. miR-194-5p predicted treatment response with an AUC of 0.831 and was an independent predictor. Mechanistically, miR-194-5p targeted SOCS2. Functional studies demonstrated that miR-194-5p overexpression enhanced, while SOCS2 supplementation attenuated, pegIFNα-induced phosphorylation of STAT1/STAT2, thereby influencing cell viability and inflammatory factor expression (TNF-α, IL-6, IL-1β).

Conclusion: miR-194-5p may predict pegIFNα response in HBeAg-positive CHB. It regulates interferon signaling by targeting SOCS2 and modulating the JAK-STAT pathway activation, suggesting the miR-194-5p/SOCS2 axis as a potential therapeutic target.

Influenza A virus remains a persistent threat, continuously evolving and contributing to seasonal epidemics and potential pandemics. In this study, we analyzed clinical samples collected from pediatric patients in Shanghai between 2022 and 2023, following the SARS-CoV-2 pandemic, to assess the genetic diversity of circulating influenza A virus strains. Out of 88 clinical samples that were positive for influenza A virus, seven isolates were successfully cultured and subjected to whole-genome sequencing. Whole-genome sequencing was performed using the Illumina high-throughput sequencing platform, while missing genomic segments, which were identified in the whole-genome sequence of isolates, were later amplified via standard PCR and Sanger sequencing. Phylogenetic analysis revealed a significant divergence between H3N2 strains from 2023 to those from 2022, suggesting a potential decline in vaccine efficacy over successive seasons. A H1N1 strain isolated from 2022 exhibited close genetic similarity to the vaccine strain. Mutational analysis identified key substitutions in the hemagglutinin and neuraminidase regions, including the I222V mutation in the neuraminidase segment of sample B623080303, which is associated with strong resistance to oseltamivir and peramivir. Another highly drug-resistant N206D mutation in the hemagglutinin region, detected in four clinical isolates, was found to alter host specificity by reducing binding affinity to human-like α2,6-linked receptors while increasing affinity for avian-like α2,3-linked receptors, thereby influencing host adaptation dynamics. The findings provide critical insights into the evolutionary trends of influenza A virus strains post-COVID-19 pandemic and their potential implications for vaccine effectiveness and antiviral resistance.