Virulence[JOURNAL]
Sun
200 papers
Antibacterial efficacy and mechanism of the novel antimicrobial peptide lachnospirin-1 against .
She P, Li M, Liu Y … +6 more , Huang G, Guo S, Xiao D, Hong Y, Lu L, Wu Y
Virulence · 2026 Dec · PMID 41838520 · Full text
The treatment of carbapenem-resistant (CRAB) infections has become a major global medical challenge; therefore, there is an urgent need for new antimicrobial development. Antimicrobial peptides hold great promising pote...
The treatment of carbapenem-resistant (CRAB) infections has become a major global medical challenge; therefore, there is an urgent need for new antimicrobial development. Antimicrobial peptides hold great promising potential due to their rapid bactericidal activity and low induction of drug resistance. In this study, we screened and synthesized the antimicrobial peptide lachnospirin-1, which exhibited significant bactericidal activity against CRAB and can also effectively eliminate its biofilms and persister cells. Mechanism studies, including fluorescent probe detection, transmission electron microscopy observations, and molecular dynamics simulations, et al. indicated that lachnospirin-1 exerts its effects through multiple mechanisms, such as disrupting bacterial cell membranes, neutralizing lipopolysaccharide, as well as inducing oxidative stress, which also demonstrates its certain potential. In addition, the favorable safety profile and effective bactericidal activity of lachnospirin-1 were determined by mouse models. Overall, our study found that lachnospirin-1 has considerable research potential as a lead compound and possesses latent value as a clinical therapy for refractory infections caused by CRAB.
Comment on "Intratumorally specific microbial-derived lipopolysaccharide contributes to non-small cell lung cancer progression".
Angelakopoulou EA, Angelakopoulou IM, Tsolaki F
Virulence · 2026 Dec · PMID 41824752 · Full text
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Functional regulation and cross-talk of type III and type VI secretion systems in .
Li X, Ding Y, Sun Y … +5 more , Gu Y, Feng W, Jia Y, Chen H, Chen S
Virulence · 2026 Dec · PMID 41824637 · Full text
In , the type III and type VI secretion systems (T3SS and T6SS) play critical roles in pathogenicity. The bacterium harbors two distinct T3SSs: T3SS-1, encoded by SPI-1, promotes host cell invasion, whereas T3SS-2 (locat...
In , the type III and type VI secretion systems (T3SS and T6SS) play critical roles in pathogenicity. The bacterium harbors two distinct T3SSs: T3SS-1, encoded by SPI-1, promotes host cell invasion, whereas T3SS-2 (located within SPI-2) facilitates systemic infection. Both systems translocate effector proteins that disrupt normal host cell functions. Meanwhile, the T6SS enhances competitive fitness in the gut by targeting rival bacteria and supports evasion of the host immune response. Recent evidence indicates that these secretion systems share common regulatory components, including the PhoP-PhoQ and PmrA-PmrB two-component systems, as well as signaling molecules such as cyclic di-GMP (c-di-GMP), allowing coordinated activation and functional adaptation during infection. However, the precise mechanisms governing their crosstalk remain poorly understood. This review summarizes the current knowledge of the composition, function, and regulation of T3SS and T6SS in Salmonella, examines their interplay, and provides perspectives for future research into pathogenesis.
Thymosin α1-induced secretion of the IL-15/RA complex by THP-1-derived dendritic cells restrains HIV latency .
Chen C, Xun J, Wang J … +8 more , Zhang R, Qi T, Liu L, Zhang X, Song Z, Shen Y, Lu H, Chen J
Virulence · 2026 Dec · PMID 41824632 · Full text
Viral reservoir presents a significant challenge in HIV-1 cure. We previously observed that Thymosin α1 (Tα1) may restrict the reservoir through the IL-15 pathway. However, the precise mechanism remains to be fully eluci...
Viral reservoir presents a significant challenge in HIV-1 cure. We previously observed that Thymosin α1 (Tα1) may restrict the reservoir through the IL-15 pathway. However, the precise mechanism remains to be fully elucidated. Peripheral blood mononuclear cells (PBMCs) were obtained from people living with HIV-1 (PLWH). In vitro, THP-1 cells were differentiated into mature monocyte-derived dendritic cells (MoDCs) and co-cultured with PBMCs under various conditions. Intracellular HIV-1 p24 levels, CD8+ T and NK cell functionality, and reservoir size were evaluated. In vitro, Tα1 stimulation of MoDCs resulted in significant immune response and secretion of IL-15/RA complex ( < 0.001). This interaction with IL-2 Rβ/γ receptors on T cells enhanced the intracellular secretion of CCL3/5, IFN-γ, and TNF-α in CD8+ T cells ( < 0.05), which inhibited p24 levels in CD4+ T cells ( = 0.002), and reduced HIV-1 integrated DNA levels ( = 0.012). Furthermore, the secretion levels of IFN-γ, TNF-α, and GZMB in NK cells and proportion of CD8+ T cells significantly increased following co-culture. These alterations were found to be markedly inversely associated with reservoir size and reactivation. However, these effects were observed in PBMCs from immunological responders (CD4+ T cell count > 350 cells/µL) rather than nonresponders. Tα1 enhances CD8+ T cell function, promotes T proliferation, and suppresses reservoir size and reactivation via IL-15 pathway activation in dendritic cells, which warrants testing in functional cure trials in the future.
The mouse gastric surface epithelial cell and its response to early infection.
Erhardsson M, Santos L, Benktander J … +3 more , Sharba S, Thorell K, Lindén S
Virulence · 2026 Dec · PMID 41824631 · Full text
infection is the main risk factor for gastric cancer. easily develop antibiotic resistance and evade host defenses. In-depth knowledge of the first barrier that encounter, the gastric surface mucus-producing epithelial...
infection is the main risk factor for gastric cancer. easily develop antibiotic resistance and evade host defenses. In-depth knowledge of the first barrier that encounter, the gastric surface mucus-producing epithelial cells (SMCs), may enable improved treatment and prevention. This study aimed to characterize SMC gene expression, mucus glycosylation, and identify how colonization affects these parameters. The glycosylation of eight -infected and eight sham control mice was characterized by mass spectrometry. SMCs from five infected and five sham control mice were extracted with laser microdissection (LCM) and sequenced with RNA sequencing (RNA-Seq). SMCs were characterized by high gene expression for proteins secreted into mucus (, , , , and , mitoribosome RNA, and cytoskeleton proteins. Mucin glycans were large, complex, heavily fucosylated, and dense with H-antigen motifs. Two main glycosylation pathways ending in H-antigen glycans were identified and corroborated with glycosyltransferase expression. Glycosylation was consistent between -infected and sham control mice. RNA-Seq data was analysed for differential gene expression, gene set enrichment analysis, and network analysis of functionally-related genes. The analyses revealed that genes required for protein synthesis and oxidative phosphorylation were down-regulated in infected mice. Most up-regulated genes were either interferon-stimulated genes or able to induce interferon production themselves. Depletion of Nkx6-3 occurred in the infected mice, indicating initiation of a pre-cancerous cascade. LCM RNA-Seq of SMCs was thus feasible and enabled characterization of the SMC and definition of a gene set showing how infection affects SMCs.
HIV-1 Vpr activates microglia by upregulating m6A modification through ubiquitin-proteasome pathway-mediated degradation of the demethylase ALKBH5.
Peng Q, Li W, Qian F … +9 more , Zhu Y, Hu S, Shi Y, Xia Y, Liu W, Shu X, Wan P, Liu Y, Sun B
Virulence · 2026 Dec · PMID 41824629 · Full text
HIV-1 infection activates microglia and triggers neuroinflammation, which is the primary cause of HIV-associated neurological complications. Our previous study demonstrated that HIV-1 infection upregulates m6A modificati...
HIV-1 infection activates microglia and triggers neuroinflammation, which is the primary cause of HIV-associated neurological complications. Our previous study demonstrated that HIV-1 infection upregulates m6A modification in microglia, and in this study, we investigated the underlying regulatory mechanisms. Through viral protein screening, we identified Vpr as the protein responsible for increasing m6A modification. Further analysis revealed that HIV-1 infection reduces the level of the m6A demethylase ALKBH5. Vpr deleted HIV-1 infection and Q65R mutant Vpr expression experiments demonstrated that Vpr is capable of degrading ALKBH5 protein via the ubiquitin-proteasome pathway by interacting with ALKBH5. Addition of m6A inhibitors or overexpression of ALKBH5 inhibited Vpr-induced microglial activation and the production of inflammatory cytokines, suggesting that the upregulation of m6A modification might play a crucial role in microglial activation induced by Vpr. As microglial activation is a major cause of neuroinflammation leading to neuronal damage, this study provides new insights for understanding the interactions between HIV-1 and microglia, and might provide new ideas for the prevention strategies study on the neuroinflammation caused by HIV-1 infection.
Analyses of receptor binding specificity of highly pathogenic avian influenza A (H5N1) viruses isolated from felines in South Korea, 2023.
Son DH, Balupuri A, Nam JH … +6 more , Kim IH, Choi YJ, An BM, Kim JM, Kim EJ, Kang NS
Virulence · 2026 Dec · PMID 41725526 · Full text
Influenza viruses infect host cells by binding to specific sialic acid receptors present on the surface of target cells, and this receptor binding exhibits specificity depending on cell type and host species. Avian influ...
Influenza viruses infect host cells by binding to specific sialic acid receptors present on the surface of target cells, and this receptor binding exhibits specificity depending on cell type and host species. Avian influenza A (H5N1) viruses typically bind preferentially to α2,3-linked sialic acid receptors, although some strains have been reported to acquire binding affinity for the human-type α2,6-linked sialic acid receptors, highlighting the need for ongoing receptor binding analyses of highly pathogenic avian influenza (HPAI) viruses. Notably, in July 2023, two distinct cases of fatal cluster infections in felines caused by HPAI H5N1 viruses were reported for the first time in South Korea (Gwanak and Yongsan). Characterization of the isolated strains revealed high pathogenicity and efficient contact transmission in mammals. In this study, we investigated the receptor binding specificity of the H5N1 viruses associated with these feline outbreaks to assess their potential threat to human health. Our findings demonstrated that both felines-derived and avian-derived H5N1 isolates retained strong binding affinity to avian-type α2,3-linked sialic acid receptors, while showing no detectable binding to human-type α2,6-linked sialic acid receptors. These results provide experimental evidence that the feline H5N1 isolates retain avian-type receptor specificity, indicating a low potential for efficient human-to-human transmission.
A hepcidin homolog from inhibits the infection of Anguillid herpesvirus 1 by interacting with the viral envelope protein ORF51.
Duan Y, Ge JQ, Meng XZ … +2 more , Chen F, Wang KJ
Virulence · 2026 Dec · PMID 41725514 · Full text
Frequent outbreaks of eel "mucus sloughing and hemorrhagic septicemia disease" caused by Anguillid herpesvirus 1 (AngHV) are a major epidemic in both wild and farmed eels. This virus has garnered global attention due to...
Frequent outbreaks of eel "mucus sloughing and hemorrhagic septicemia disease" caused by Anguillid herpesvirus 1 (AngHV) are a major epidemic in both wild and farmed eels. This virus has garnered global attention due to heavy losses on eel farms and the lack of protective vaccines or effective drugs, highlighting the urgent need for potent antiviral agents. In this study, we revealed a hepcidin homolog LJ-hep2 from Japanese seabass () can bind to AngHV and impede viral entry into cells. LJ-hep2 could directly destroy the viral envelope and showed a higher anti-AngHV activity than AA-hep (a hepcidin homolog cloned from ). It was found that the destruction of viral structure by LJ-hep2 was related to the binding of the peptide to AngHV envelope protein ORF51, and the two amino acid residues at the N-terminus of the peptide (lysine and phenylalanine) might play a key role. Comparative antiviral experiments with mutated LJ-hep2 (LJ-hep2) and multi-species hepcidin further confirmed this finding and demonstrated that these two amino acids were indispensable in the inhibition of AngHV infection by LJ-hep2. In an established eel immersion infection model, LJ-hep2 treatment reduced viral accumulation in tissues, inhibited horizontal transmission, alleviated skin lesions, and improved eel survival. Taken together, this study suggests that LJ-hep2 could inhibit AngHV infection and , and identify ORF51 as a potential target for the development of anti-AngHV drugs.
Substrate secretion by different EHEC secretion systems during their interaction with epithelial cells.
Zambrano-Arguello L, Vazquez-Lopez J, Navarro-Garcia F
Virulence · 2026 Dec · PMID 41709771 · Full text
Enterohemorrhagic (EHEC) causes severe foodborne illness in humans. EHEC harbors five types of secretion systems (SSs) and unlike the type three secretion system (T3SS), the other SSs are less explored. Some substrates...
Enterohemorrhagic (EHEC) causes severe foodborne illness in humans. EHEC harbors five types of secretion systems (SSs) and unlike the type three secretion system (T3SS), the other SSs are less explored. Some substrates secreted by these SSs have been described; however, how these SSs collectively participate in EHEC-epithelial cell interaction during infection remains unknown. Here, we optimized protein secretion by four of the EHEC SSs in the absence and presence of epithelial cells, since the T6SS is not expressed . The secretion of substrates through the EHEC SSs followed a hierarchical pattern when bacteria encountered epithelial cells. Epithelial cells increase the protein secretion by EHEC and mutants in SSs (Western-blot and proteomics). Remarkably, mutants in one particular SS affect protein secretion by other SSs. Analysis of the EHEC secretome in the absence/presence of cells vs different SS mutants showed that epithelial cells increase the abundance of specific substrates; the lack of one SS affects the secretion by other SSs; epithelial cells diminish the effects caused by mutating some SS; bioinformatics analyses identified new potential substrates for each SS. Western blot analysis validated the interdependence in substrate secretion between SSs. Consequently, a complex interaction exists between SSs during epithelial cell infection, affecting the epithelial cells-bacteria interaction and the EHEC pathogenesis.
Platelet-Neutrophil interactions in invasive syndrome: The role of aspirin.
Lin YT, Chang CC, Chen FJ … +1 more , Lee CH
Virulence · 2026 Dec · PMID 41709754 · Full text
invasive syndrome (KPIS), often arising from pyogenic liver abscesses, is characterized by metastatic infections and thrombotic complications. Diabetes mellitus (DM) is the most important risk factor for KPIS, as hypergl...
invasive syndrome (KPIS), often arising from pyogenic liver abscesses, is characterized by metastatic infections and thrombotic complications. Diabetes mellitus (DM) is the most important risk factor for KPIS, as hyperglycemia promotes resistance of hypervirulent ;(hvKp) strains to phagocytosis and impairs neutrophil function. Given the interplay between platelet activation, inflammation, and thrombosis, aspirin, a well-established antiplatelet agent, has been associated with reduced incidence and recurrence of pyogenic liver abscesses in cohort studies. Platelets interact with neutrophils to form platelet - neutrophil aggregates (PNAs), which may contribute to KPIS pathogenesis. This study examined platelet - neutrophil interactions under hyperglycemic conditions using assays and models of diabetic mice infected with hvKp. High glucose concentrations significantly increased platelet activation, PNA formation, and bacterial survival. Salicylic acid, the bioactive metabolite of aspirin, reduced platelet activation and bacterial burden but did not impede PNA formation. Aspirin pre-treatment improved survival, reduced organ abscesses, and preserved tissue integrity in diabetic mice infected with hvKp. These results highlight the relationship between hyperglycemia, platelet activation, and immune dysregulation in KPIS, and support aspirin as a potential adjunctive therapy to mitigate thromboinflammatory complications of hvKp infection.
The cyclin dependent kinase (CDK)7 inhibitor BS-181 inhibits pathogenic Cryptococcus species, causing G/M arrest and a splicing defect.
Sethiya P, Desmarini D, Bowring B … +7 more , Dinh H, Cain AK, Parsania C, Halliday CL, Chen SC, Hewitt K, Djordjevic JT
Virulence · 2026 Dec · PMID 41701636 · Full text
The fungal priority pathogen and basidiomycete, , causes lung and brain infection in predominantly immuno-compromised individuals and there is an urgent need for new treatment options. The pyrazolopyrimidine-based cyclin...
The fungal priority pathogen and basidiomycete, , causes lung and brain infection in predominantly immuno-compromised individuals and there is an urgent need for new treatment options. The pyrazolopyrimidine-based cyclin dependent kinase (CDK)7 inhibitor, BS-181, has anticancer properties, but its antifungal activity has not been investigated. We show that cryptococcal CDK7 more closely resembles the human enzyme than that of ascomycetes, and that BS-181 inhibits its activity. BS-181 inhibited growth of both and (), but not ascomycete fungi and delayed progression through the G/M phase of the cell cycle. Transcriptomic analysis revealed that BS-181 induces splicing defects leading to elevated intron retention within the transcriptome and also suppresses translational processes. BS-181 displayed additive or synergistic activity with licensed antifungals against laboratory and clinical and strains, most notably with amphotericin B where synergy (2-4-fold reduction in the amphotericin B MIC) was achieved using low-sub micromolar concentrations of BS-181. Compared with either drug alone, BS-181-AmB combination therapy provided greater protection against infection in a wax moth model ( ≤ 0.032) and extended survival of -infected mice. These findings demonstrate that CDK7 inhibitors, already of interest as anticancer agents, could be repurposed to prevent or treat opportunistic fungal infections in cancer patients when combined with licensed antifungals limited by either toxicity or resistance.
Peste des petits ruminants virus (PPRV) modulates caprine dendritic cell function and induces immunosuppression through IL-10 upregulation.
Nogales-Altozano P, Martínez-Rodrigo A, Rojas JM … +1 more , Sevilla N
Virulence · 2026 Dec · PMID 41693562 · Full text
Peste des petits ruminants (PPR) is a WOAH notifiable disease affecting sheep and goats, caused by Peste des petits ruminants virus (PPRV), a morbillivirus of the family. Infection with PPRV leads to immunosuppression,...
Peste des petits ruminants (PPR) is a WOAH notifiable disease affecting sheep and goats, caused by Peste des petits ruminants virus (PPRV), a morbillivirus of the family. Infection with PPRV leads to immunosuppression, creating conditions for opportunistic infections that can result in animal mortality. Although goats generally exhibit more severe clinical signs than sheep, the underlying mechanisms driving this species-specific difference remain poorly understood. Dendritic cells (DC), which play a pivotal role in initiating immune responses, are among the immune targets of PPRV in small ruminants. In this study, we examined the impact of PPRV on caprine immune cells, focusing on CD14 monocytes and monocyte-derived dendritic cells (MoDC). Our findings indicate that PPRV infects goat monocytes without preventing their differentiation into DC. Infected MoDC displayed increased expression of maturation markers and reduced phagocytic activity, suggesting a transition toward an activated phenotype. However, mixed lymphocyte reaction assays revealed that PPRV-infected MoDCs have a diminished capacity to promote T cell proliferation. This impaired function was associated with elevated IL-10 production and reduced conjugation between DCs and T cells. Overall, PPRV infection induces an atypical maturation stage in goat MoDCs, characterized by partial activation but impaired antigen presentation. These findings demonstrate that PPRV-driven modulation of DC function contributes to the immunosuppression observed during PPRV infection in goats.
Virulence of and relatives using the model.
Zhou S, Ahmed SA, Abd Algaffar SO … +4 more , Ismail MAI, van der Lee H, Kang Y, de Hoog GS
Virulence · 2026 Dec · PMID 41685886 · Full text
section encompasses multiple species, with being significant for human health because of its dual role as a major aflatoxin producer and opportunist. However, the mechanisms underlying its virulence remain incompletely...
section encompasses multiple species, with being significant for human health because of its dual role as a major aflatoxin producer and opportunist. However, the mechanisms underlying its virulence remain incompletely understood. This study evaluates the pathogenic potential of and its relatives using the infection model. Twenty-six isolates (clinical and environmental) and 17 relatives/domesticated species were tested in , with larval survival monitored over 7 d. Histology, direct microscopy, and culture were used to validate the infection. Growth kinetics and spore sizes were measured to evaluate correlations with pathogenicity. All isolates demonstrated high virulence, causing 90%, and 100% mortality of larvae within 3 and 7 d, respectively, with no significant differences between sources. Aflatoxin-producers exhibited higher virulence, resulting in 100% mortality of larvae within 5 d ( < 0.05). Related species exhibited lower virulence; larval mortalities ranging from 20% to 70% within 3 d, ranked as > > > > > . Growth kinetics and spore size were correlated with virulence, as rapid growth and smaller spores were associated with increased pathogenicity. exhibits higher virulence than its relatives, with growth rate, and spore size influencing pathogenicity. The model proves effective for comparative virulence studies. These findings highlight the potential health risks of , including its domesticated relatives used in food fermentations, necessitating further investigations into their pathogenic potential.
Compound probiotics alleviate -induced diarrhea in calves by modulating tryptophan and bile acid metabolism of the fecal microbiota.
Zhong J, Tang J, Han L … +3 more , Wang W, Zhang X, Zhang S
Virulence · 2026 Dec · PMID 41669940 · Full text
Calf diarrhea, particularly that caused by diarrheagenic , has become a major issue affecting the sustainable development of the calf farming industry. Although the use of traditional antimicrobial agents can alleviate s...
Calf diarrhea, particularly that caused by diarrheagenic , has become a major issue affecting the sustainable development of the calf farming industry. Although the use of traditional antimicrobial agents can alleviate symptoms, challenges such as antibiotic resistance, drug residues, and intestinal microbiota dysbiosis urgently need to be addressed. Therefore, this study investigates the mechanism by which compound probiotics alleviate diarrheagenic -induced diarrhea in calves. Compound probiotics were administered to calves with diarrheagenic -induced diarrhea, and their effects on growth performance, intestinal microbiota structure, and metabolic profiles were evaluated. The results showed that compound probiotic intervention significantly improved calf growth performance and weight gain. Integrated 16S rRNA sequencing and metabolomics analyses revealed that compound probiotic intervention markedly modulated the intestinal microbiota, particularly by increasing the abundance of the genus , while also improving tryptophan and bile acid metabolic pathways. Furthermore, fecal microbiota transplantation experiments conducted in both calves and antibiotic-induced microbiota depletion mouse models confirmed the regulatory effects of compound probiotics on the intestinal microbiota, especially with respect to tryptophan and bile acid metabolism. Compound probiotic intervention regulated key metabolites, including kynurenic acid, taurodeoxycholic acid, and ursodeoxycholic acid, which were positively correlated with , and significantly reduced inflammation by downregulating pro-inflammatory factors and upregulating anti-inflammatory factors, thereby alleviating diarrheagenic -induced diarrhea in calves. Overall, this study provides new insights into the application of probiotics in intestinal health management and highlights the significant potential of compound probiotics as an alternative to antibiotics for the treatment of calf diarrhea.
Gut microbiota-driven IL-17A production by hepatic γδ T cells enhances neutrophil defense against systemic infection.
Pan N, Su X, Meng Y … +4 more , Liang Y, Chen X, Zhang H, Wang X
Virulence · 2026 Dec · PMID 41657029 · Full text
() 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 mechan...
() 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 bloodstream infection using animal models. Our findings demonstrate that the gut microbiota exerts a protective effect against systemic 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 ( activates this hepatic γδT17-neutrophil axis, enhancing host defense against 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 infections.
Machine learning prediction of functional cure to pegylated interferon-alpha therapy in two HBV populations: Advantaged populations and HBeAg-negative patients.
Li J, Li H, Lin C … +7 more , Jiang R, Wang L, He Y, Yang X, Gong K, Xun Z, Zheng Q
Virulence · 2026 Dec · PMID 41656920 · Full text
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 identif...
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.
PLIN3-triggered lipophagic flux releases FFAs to facilitate CSFV propagation.
Li B, Zou L, Sun C … +12 more , Jiang J, Li S, Wang J, He Y, Qin Y, Zeng S, Song Y, Zeng W, Yi L, Fan S, Chen J, Wu K
Virulence · 2026 Dec · PMID 41656915 · Full text
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 regulator...
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 Hepatic stellate cells(HSCs)and upregulates perilipin3(PLIN3) expression, a LD-associated protein that facilitates viral replication. Further studies demonstrated that PLIN3 activates the AMPK signaling pathway to promote lipophagy-mediated FFAs 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.
inhibits classical swine fever virus replication by targeting the -regulated AMPK/mTOR autophagy pathway.
Wang X, Yang S, Xie L … +8 more , Qi S, Gao L, Li Y, Li Q, Bi J, Liu J, Li Y, Yin G
Virulence · 2026 Dec · PMID 41656913 · Full text
Classical swine fever virus (CSFV) remains a major threat to the global swine industry, yet the involvement of host miRNAs in its pathogenic mechanisms is not fully understood. In this study, we demonstrate for the first...
Classical swine fever virus (CSFV) remains a major threat to the global swine industry, yet the involvement of host miRNAs in its pathogenic mechanisms is not fully understood. In this study, we demonstrate for the first time that inhibits CSFV replication through an autophagy-dependent mechanism by targeting polycystin-2 (), a key calcium channel protein that regulates the AMPK/mTOR signaling pathway. Using the PK-15 cell model, we found that CSFV infection significantly upregulates expression. Functional assays revealed that exerts antiviral effects by directly binding to the 3'-UTR of , as confirmed by bioinformatics prediction and dual-luciferase reporter assays. Silencing of recapitulated the antiviral effect of overexpression, while reconstitution restored viral replication by activating AMPK signaling and suppressing mTOR activity, thereby significantly enhancing autophagic flux - as evidenced by increased LC3-II/I ratio and decreased p62 levels. Mechanistically, regulates intracellular calcium dynamics, modulating the AMPK/mTOR-autophagy axis to promote CSFV proliferation. This work uncovers a novel host antiviral mechanism in which a miRNA controls virus-induced autophagy via calcium signaling. To our knowledge, this is the first report to establish the pivotal role of miRNA-mediated calcium signaling modulation in flavivirus-host interactions. These findings provide a mechanistic framework and potential therapeutic targets for anti-CSFV interventions focused on or autophagy regulation.
Beyond a single species: Mapping virulence traits across the redefined complex.
Wolf M, Scholz KJ, Al-Ahmad A … +5 more , Steinberg T, Kruse A, Rezasoltani S, Cieplik F, Conrads G
Virulence · 2026 Dec · PMID 41656911 · Full text
was long regarded as a single species and later subdivided into four subspecies (). In 2022, these subspecies were validated as separate species and further members of the complex have been proposed ( sp. nov.). Given t...
was long regarded as a single species and later subdivided into four subspecies (). In 2022, these subspecies were validated as separate species and further members of the complex have been proposed ( sp. nov.). Given the increasing evidence linking to various diseases, identifying (sub-)species-specific virulence factors has become essential. Infection in mammalian hosts depends on virulence factors that can be surface-exposed, released into the extracellular environment, or injected directly into host cells. This narrative review aims to address the different pathogenic potentials of each former subspecies. These differences range from adhesin diversity and metabolic adaptations, the repertoire of ABC transporters, lyases and type IV conjugative pili to the capability to invade tissues, evade the immune system and form biofilms and outer membrane vesicles.
LeuO fine-tunes the virulence attributable to pathogenicity island-2 via repressing transcription in Typhimurium.
Kim E, Yoon H
Virulence · 2026 Dec · PMID 41649349 · Full text
LeuO, initially identified as a leucine regulator in , has since been identified as a global regulator required for bacterial pathogenicity in a broad range of bacteria, including , , and . This study aimed to determine...
LeuO, initially identified as a leucine regulator in , has since been identified as a global regulator required for bacterial pathogenicity in a broad range of bacteria, including , , and . This study aimed to determine the regulatory role of LeuO in pathogenicity island (SPI)-2, essential for the intracellular proliferation of serovar Typhimurium (. Typhimurium). Overexpression of LeuO repressed the transcription of SPI-2 genes and accordingly decreased its protein levels. Chromatin immunoprecipitation sequencing revealed the genome-wide binding sites of LeuO in . Typhimurium 14,028 and identified a distinctive 23-nucleotide motif with high similarity to that previously discovered in . Notably, multiple LeuO-binding sites were predicted within SPI-2, primarily adjacent to the and loci. binding assays verified the high binding affinity between LeuO and three specific motifs located at positions -35 to -12 (),+231 to + 254 () near , and at positions -622 to -599 () near , relative to their transcription start sites. Furthermore, LeuO overexpression abolished the transcription of fused to the promoter containing and , suggesting the direct repression of via LeuO-binding. The absence of LeuO increased the intracellular survival of . Typhimurium within macrophages, whereas its overexpression attenuated bacterial replication, which was presumably associated with the downregulation of SPI-2 by LeuO. This study reveals the versatile regulatory mechanisms of LeuO and underscores its pivotal role in modulating SPI-2 expression, thereby providing key insights into the fine-tuning of virulence by during systemic infection.
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