Virulence最新文献

Small extracellular vesicles (sEVs) play a role in the pathophysiology of viral respiratory infections and may be suitable biomarkers for COVID-19 and Influenza infections, or targets for treatment. We investigated differences in the surface proteome of plasma sEVs in patients with COVID-19 and Influenza. In a discovery cohort with 117 patients, we used a random forest (RF) classifier in order to discriminate COVID-19 and Influenza patients based on routine clinical parameters. Furthermore, plasma samples from these patients were analyzed with an EV Array containing 33 antibodies to capture sEVs, which were then visualized with a combination of CD9, CD63, and CD81 antibodies. We applied an RF classifier and a random depth-first search (RDFS) approach to extract markers with the best discriminatory potential. Data were then validated in an independent set of patient samples on a chip-based ExoView platform.In the initial cohort of 117 patients, leukocyte numbers, and heart rate discriminated best between COVID-19 and Influenza infection. In the plasma samples, 32 EV surface markers could be detected. Feature panels containing CD9, CD81, and CD141 allowed a discrimination between COVID-19 and Influenza. Consecutively, increased CD9 abundance was validated in a second, independent cohort, with the ExoView technology. The increased CD9 signal in Influenza patients was confirmed and shown to be mostly driven by CD9/CD41a double positive sEVs, hinting at a thrombocyte origin.We identified leukocyte numbers and heart rate, as well as CD9 as a sEV surface marker to differentiate COVID-19 from Influenza patients.

Mycoviruses are increasingly recognized for their potential applications in crop protection, particularly in biocontrol of phytopathogenic fungi and in enhancement of the environmental competence and virulence of entomopathogenic ascomycetes (EA) to optimize their pest control potential. Here, we provide the first evidence of a functional switch between insect-pathogenic and nonpathogenic states in a strain of the EA Beauveria bassiana, driven by a Beauveria bassiana victorivirus 1 (BbVV-1) acting as an essential virulence determinant. The mycovirus-infected wild-type strain (WMI) demonstrated broad-spectrum virulence across insect orders, whereas the isogenic mycovirus-free strain (MFr) was entirely nonpathogenic, exhibiting a complete suppression of cuticle penetration capability, which was restored only through injection of conidia into the hemocoel, bypassing the cuticle barrier. A comprehensive analysis of mycovirus-related inhibition of cuticle penetration revealed that WMI exhibited strong activity in extracellular cuticle-degrading enzymes (ECEs) relevant to virulence, with emphasis on Pr1 protease, whereas ECE secretion, and notably Pr1, were markedly suppressed in MFr. Insect infection by WMI showed a time-dependent increase in the number of pr1 gene copies and quantity of fungal DNA, while neither pr1 expression nor fungal DNA were detected in MFr during the infection cycle. Downregulation of the pr1 gene in MFr suggests a direct effect of mycovirus on fungal transcriptional regulation, highlighting the potential to deploy this BbVV-1 to produce hypervirulent EA strains but also to transition EA from entomopathogens to solely plant-beneficial microorganisms.

Influenza H3N8 viruses have been frequently isolated from chicken farms. However, comprehensive characterization of their virological properties, molecular evolution, virulence, and risk of spillover into mammals remains limited. In particular, little attention has been given to the transmission efficiency of H3N8 avian influenza viruses among chickens and their spillover risk. Here, we systematically characterized H3N8 isolates obtained from asymptomatic chickens through multidisciplinary approaches, including genomic surveillance, receptor binding profiling, and in vivo pathogenicity and transmission assays. All strains showed >98% nucleotide homology with human-infecting strains. Phylogenetic analysis revealed that their internal genes were derived from H9N2, while HA and PB2 genes shared high homology (bootstrap support >98%) with the novel H3N3 virus. All isolates maintained avian-type receptor-binding motifs (HA-Q226/G228) while exhibiting dual α2,3/α2,6-sialic acid binding and robust replication in mammalian cells (peak MDCK titer: 10⁷·⁵ TCID₅₀/mL). ZJ07 demonstrated exceptional thermostability (HA activity persisting >3 hr at 56°C), while JS13 showed 1.8-fold elevated neuraminidase activity versus controls (p < 0.05). In vivo, all strains caused subclinical infections with broad tissue tropism in chickens and mice without adaptation, transmitting efficiently among direct-contact poultry. Strikingly, AH12 achieved 100% airborne transmission in chickens. These findings confirm H3N8's capacity for silent poultry circulation and identify key features conducive to cross-species infection, including dual receptor binding, infection in a mammalian model, and high genetic homology with human strains. The airborne transmissibility of AH12 underscores a heightened spillover risk, necessitating enhanced surveillance and vaccines targeting avian-human interface strains.

The emergence and global spread of antimicrobial resistant (AMR) pathogens represent a critical challenge to global public health security. The ESKAPE pathogens refer to a group of highly troublesome multidrug-resistant bacteria responsible for hospital-acquired infections. Of particular concern are Gram-negative ESKAPE pathogens, which pose a significant threat to patient health and healthcare systems worldwide. Systematic investigation into antimicrobial resistance mechanisms and pathogenicity regulation is therefore imperative for developing effective infection control strategies. Emerging evidence highlights small regulatory RNAs (sRNAs) as pivotal post-transcriptional modulators in bacterial physiology, particularly in governing virulence determinant expression and host-pathogen interactions during infection. This review summarizes recent advances in sRNA-mediated regulatory mechanisms in Gram-negative ESKAPE pathogens, with emphasis on Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa. We discuss the classification of sRNAs, their regulatory mechanisms, their roles in modulating virulence factors and pathogenicity, as well as the challenges and opportunities in targeting sRNAs for antimicrobial therapy. Evidence accumulated across the studies reviewed indicates that sRNAs exert their function through base pairing with target mRNAs or other sRNA, through interactions with proteins, or as dual-function sRNA. sRNAs have emerged as essential regulators of virulence in the ESKAPE pathogens, influencing capsular polysaccharide production, iron acquisition, biofilm formation, regulation of catabolic pathway genes, cell adhesion and invasion, as well as host immune responses during infection. This review provides a framework for understanding bacterial adaptive evolution through sRNA-mediated regulation and identifies novel intervention targets against multidrug-resistant pathogens.

Gut microbiota has been considered as a key bridge between phytochemicals and host immunity. Prevotella copri (P. copri) showed a close correlation with inflammation, and protocatechuic acid (PCA) has potential protective effects in our previous studies. To understand the underlying mechanism, a total of 108 healthy Duroc × Landrace × Yorkshire weaned piglets, aged 21 d, were randomly assigned into 3 groups, with 6 replicates and 6 piglets per replicate. The piglets were fed a basal diet, a basal diet containing 1.0 × 10⁸ CFU/kg P. copri or 1.0 × 10⁸ CFU/kg P. copri +400 mg/kg PCA for 28 d. Results showed that P. copri decreased the final body weight and average daily gain (ADG), while increased the feed-to-gain ratio (F/G), with increased serum levels of interleukin (IL)-2 and IL-8 in piglets (p < 0.05), and reduced the expression of intestinal tight junction protein (p < 0.05). Dietary supplementation of PCA increased the ADG by suppressing inflammation and enhancing intestinal integrity. In vitro experiments demonstrated that argininosuccinic acid, indole-3-aldehyde, and N-acetylputrescine are critical metabolites produced by P. copri, which initiated inflammatory responses by upregulating pro-inflammatory cytokines and downregulating tight junction proteins in MODE-K cells. PCA was found to effectively attenuate these effects in a dose-dependent manner. In conclusion, PCA can improve the growth performance in weaned piglets by attenuating inflammation caused by P. copri and its metabolites.

Novel goose parvovirus (NGPV) infection in ducklings induces short beak and dwarfism syndrome (SBDS), leading to significant economic losses. Since NGPV predominantly infects ducklings, whether reshaping the intestinal flora of ducklings through fecal microbiota transplantation from adult ducks (FMT-A) can alleviate SBDS is an interesting question. This study aimed to investigate the impact of FMT-A on the susceptibility of ducklings to NGPV infection, to elucidate the potential relationship between gut microbiota and viral pathogenicity. The results showed that ducklings were more susceptible to NGPV than adults, and that adult ducks exhibited higher fecal microbiota richness and diversity. FMT-A treatment attenuated NGPV-induced reductions in body weight, beak and tibia length, and muscle mass. Furthermore, FMT-A alleviated gut dysbiosis and intestinal tissue damage, increased glycogen in the intestinal mucosa, upregulated ZO-1 expression, expanded the epiphyseal region, and reduced osteoclast numbers in the tibia of ducklings. Moreover, FMT-A suppressed the expression of the Th17 cell-specific transcription factor retinoic acid receptor-related orphan receptor γt in the ileum and bone, and decreased the expression levels of pro-inflammatory cytokines in the ileum, bone, and serum. These findings indicate that ducklings are more susceptible to NGPV than adult ducks, with significantly lower diversity and abundance of fecal microbiota. FMT-A can stabilize intestinal flora, mitigate intestinal barrier damage, inhibit Th17 cell differentiation, thereby reducing abnormal bone development, and ultimately alleviate SBDS in ducklings. These findings provide a theoretical basis for developing novel strategies targeting gut microbiota modulation to prevent and control SBDS in ducklings.

Recent large-scale outbreaks of diarrhea in pigs in China have been attributed to viral pathogens. To investigate the primary viral causes of diarrhea, we collected 1343 fecal samples from 84 pig farms across 20 provinces. PEDV showed the highest positivity rate at 50.90%, with a positive farm rate of 66.67%. PoRVA had a positive rate of 33.80% and a positive farm rate of 40.48%. TGEV and PDCoV exhibited lower positivity rates of 3.10% and 6.00%, respectively, with positive farm rates of 14.29% and 16.67%. Co-infections, primarily involving PEDV and PoRVA, accounted for 19.05% of cases. Additionally, an analysis of the spatiotemporal distribution of viruses from 2022 to 2024 was conducted. This study also included phylogenetic and amino acid analyses focusing on PEDV and PoRVA. Among them, PEDV predominantly belongs to GIIa and GIIc, while PoRVA predominantly belongs to G4, G5 and G9. We analyzed neutralizing epitopes and functional sites of the PEDV S protein, revealing that the SS2 and SS6 epitopes are relatively conserved, while various mutations were observed in other functional sites. Additionally, significant variability in the VP7 protein of PoRVA was noted among different genotypes, with several conserved amino acid sequences identified, primarily located in the loop regions of the VP7 protein. The study helps identify high-risk areas and peak periods, thereby providing guidance for epidemic early warning and resource allocation. Additionally, the study conducted a further analysis of the antigenic epitopes of PEDV and PoRVA, providing important information for vaccine design and the formulation of immunization strategies.

Staphylococcus aureus (S. aureus) bloodstream infections pose a significant clinical threat, exacerbated by increasing antibiotic resistance and high mortality. While the gut microbiota is recognized as a key modulator of systemic immunity, the mechanisms underlying its protective role against invasive bacterial infections remain incompletely understood. Here, we investigated how gut microbiota influences hepatic immune responses during early S. aureus bloodstream infection using animal models. Our findings demonstrate that the gut microbiota exerts a protective effect against systemic S. aureus infection. Specifically, commensal microbiota-derived signals prime hepatic γδ T cells for rapid interleukin-17A (IL-17A) production upon bacterial challenge. This microbiota-dependent IL-17A response subsequently promotes neutrophil recruitment to the liver, facilitating bacterial clearance and limiting systemic dissemination. Disruption of the gut microbiota impaired hepatic γδ T cell IL-17A production, reduced neutrophil mobilization, and compromised host resistance to infection. Notably, we found that colonization with the commensal Limosilactobacillus reuteri (L. reuteri) activates this hepatic γδT17-neutrophil axis, enhancing host defense against S. aureus as a mechanism involving indole metabolites. This study reveals a novel gut-liver axis whereby intestinal microbiota orchestrates hepatic γδ T cell function to establish an early immunological barrier against invasive bacterial pathogens, offering potential therapeutic avenues for enhancing host defense against life-threatening S. aureus infections.

Despite advances in antiviral therapy, the rate of functional cure for chronic hepatitis B (CHB) remains unsatisfactory, and developing an applicable prediction model is pivotal to improving it. Thus, we aimed to identify key predictive factors and develop prognostic models for functional cure in HBeAg-negative patients and the advantaged populations. This retrospective study included 202 HBeAg-negative CHB patients (114 classified as advantaged populations) receiving pegylated interferon-alpha (PEG-IFNα) therapy for model derivation and internal validation, and 183 HBeAg-negative CHB patients (117 classified as advantaged populations) for model external validation. Using 48 routinely collected clinical indicators, we constructed prediction models through LASSO regression followed by multivariable logistic regression. Two nomogram-based models were developed: the SHAN model, based on four independent predictors - ln (HBsAg +1), age, neutrophil percentage (NE%), and sex - was tailored for HBeAg-negative patients. For the advantaged populations, two additional variables - alpha-fetoprotein (AFP) and lactate dehydrogenase (LDH) - were incorporated into the FLASH-N model. Both models demonstrated strong discrimination, with AUCs of 0.908 in the training set and 0.949 in the test set for the SHAN model and an AUC of 0.920 (bootstrap-corrected to 0.889) for the FLASH-N model in the advantaged populations. In external validation, SHAN model achieved an AUC of 0.861, and FLASH-N achieved an AUC of 0.800. Calibration plots and decision curve analysis further confirmed the robustness, accuracy, and clinical utility of both nomograms. By leveraging routinely available baseline variables, these models offer powerful tools for predicting functional cure in CHB, enabling refined risk stratification and more personalized clinical decision-making.

Viruses hijack host metabolic resources for replication. Previous studies have shown that classical swine fever virus (CSFV) infection induces host lipid metabolic reprogramming.However, research into the exact regulatory mechanisms between CSFV and lipid metabolism remains limited. Lipophagy refers to the degradation of lipid droplet contents to release free fatty acids(FFAs), CSFV induces autophagy to promote its replication, the regulatory mechanism between CSFV and lipophagy is unclear. In this study, we found that lipid droplets(LDs) initially accumulate and then decrease following CSFV infection. Autophagy activity was negatively correlated with lipid drople levels. Subsequent experiments revealed that CSFV induces lipophagy in HSCs (Hepatic stellate cells)and upregulates PLIN3(perilipin 3) expression, a LD-associated protein that facilitates viral replication. Further studies demonstrated that PLIN3 activates the AMPK signaling pathway to promote lipophagy-mediated free fatty acid (FFA) release. This FFA increase could be blocked by autophagy inhibitors. Notably, exogenous FFA addition reversed the shPLIN3-induced impairment of CSFV replication. Overall, this finding provides new insights into the mechanisms of virus-host lipid metabolism interactions.