Virulence[JOURNAL]
Sun
200 papers
Phosphatidylcholine biosynthesis via ChoC is crucial for cellular integrity and virulence in .
Carrillo-Marín P, Tahiri G, Camuña-Pardo L … +6 more , Lax C, Sanchis M, Capilla J, Navarro E, Garre V, Nicolás FE
Virulence · 2026 Dec · PMID 41989847 · Full text
is an opportunistic fungal pathogen and a prominent etiological agent of mucormycosis, a life-threatening invasive fungal infection. In this study, we investigated the role of , a gene encoding a putative phospholipid me...
is an opportunistic fungal pathogen and a prominent etiological agent of mucormycosis, a life-threatening invasive fungal infection. In this study, we investigated the role of , a gene encoding a putative phospholipid methyltransferase involved in phosphatidylcholine (PC) biosynthesis through the Bremer-Greenberg pathway. Deletion of using CRISPR-Cas9 led to severe defects in growth and asexual development, which persisted even at 37°C, a temperature relevant to host infection. Supplementation with choline or its precursor PDEA restored growth, confirming the importance of in maintaining PC levels. Lipidomic and transcriptomic analyses revealed broad disruptions in PC and phosphatidylethanolamine (PE) levels, glycerol-3-phosphate and fatty acid metabolism, endoplasmic reticulum (ER) stress responses, and vesicle trafficking. Notably, mutants exhibited reduced melanin and chitin content, while ergosterol levels remained unaffected, indicating specific impairment in cell envelope assembly. In a murine infection model, the mutant showed attenuated virulence, linking lipid imbalance to impaired host adaptation. Together, these findings highlight as a key regulator of membrane homeostasis and fungal pathogenicity. As the methylation-dependent PC synthesis pathway is barely present in human tissues, represents a promising target for selective antifungal therapies.
Phosphorylation of a novel STK substrate SstP1 links SUF Fe-S cluster biogenesis to oxidative stress resistance and virulence in .
Ren S, Yin H, Wang Y … +8 more , Yan R, Jia X, Li Z, Li Y, Tian Y, Peng L, Li J, Fang R
Virulence · 2026 Dec · PMID 41984734 · Full text
Iron-sulfur (Fe-S) clusters are ancient prosthetic groups that are incorporated into apoproteins to generate fully functional Fe-S proteins, representing a conserved regulatory pathway in both Eukarya and Prokaryotes. In...
Iron-sulfur (Fe-S) clusters are ancient prosthetic groups that are incorporated into apoproteins to generate fully functional Fe-S proteins, representing a conserved regulatory pathway in both Eukarya and Prokaryotes. In bacteria, the sulfur utilization factor (SUF) system mediates Fe-S cluster biosynthesis under stress conditions, thereby supporting essential metabolic processes to resist oxidative stress. In this study, we identify a novel substrate of serine/threonine kinase (STK), the protein with a DUF1831 domain (named as SstP1) in . GST pull-down and enzymatic activity assays demonstrated that STK-dependent phosphorylation of SstP1 at residue threonine 35 is required to sustain SUF-dependent Fe-S cluster biosynthesis under oxidative stress through direct interaction with the scaffold protein SufB. Functional analyses revealed that both deletion of (Δ) or introduction of a phospho-ablative T35A mutant impaired bacterial growth and markedly reduced survival under oxidative stress and iron limitation conditions. In a mouse infection model, both the Δ and T35A mutants exhibited significantly reduced bacterial burdens in the blood, lung, spleen, and brain, accompanied by attenuated virulence compared to the WT, phospho-mimetic T35E, and complementary (CΔ mutants. Collectively, these findings reveal that STK-mediated phosphorylation of SstP1 at Thr35 is essential for oxidative stress resistance and virulence in , uncovering a novel mechanism that links phosphorylation signaling to SUF-dependent Fe-S cluster biosynthesis in bacterial pathogenesis.
Isolation and characterization of a red panda amdoparvovirus causing fatal respiratory disease: Identification of VP2-S447 as a key determinant of acute lung injury.
Yang L, Nie L, Ren H … +9 more , He H, Yuan H, Yang Z, Yang K, Li W, Wang X, Zhang XX, Song Y, Yuan ZG
Virulence · 2026 Dec · PMID 41979076 · Full text
Surveillance and control of wildlife-borne pathogens are essential for preventing cross-species transmission. Ongoing diversity in Aleutian virus infection among small carnivoran has expanded host range and promoted vira...
Surveillance and control of wildlife-borne pathogens are essential for preventing cross-species transmission. Ongoing diversity in Aleutian virus infection among small carnivoran has expanded host range and promoted viral adaptation, leading to the emergence of previously unknown mutations as the virus spreads across geographic and species boundaries. In this study, we report the first isolation and characterization of a highly pathogenic red panda amdoparvovirus (Designated as RpAPV-Gd1) from a fatal case in a captive red panda () in China. Histopathological examination and in situ hybridization revealed systemic viral infection, characterized by severe acute interstitial pneumonia, multi-organ inflammation, and a marked tropism for alveolar epithelial cells. Phylogenetic analysis showed that RpAPV-Gd1 clustered closely with other red panda amdoparvovirus 2 (RpAPV-2, ), sharing 95.4% whole-genome identity. The virus exhibited broad in vitro cell tropism, including human cell lines (U937 and THP-1). In BALB/c mice, RpAPV-Gd1 caused 100% mortality, which was associated with cytokine storm and severe lung injury. Using reverse genetics, we identified a single amino acid substitution in the VP2 protein (S447R) as a critical determinant of pulmonary pathogenicity in the BALB/c mouse model. Viruses carrying the S447R mutation showed attenuated virulence and reduced replication efficiency . These findings further highlight that VP2 plays a key role in disease severity.
Serology survey against multiple SARS-CoV-2 variants of residents in Tainan, Taiwan.
Hsu IL, Du PX, Chou TM … +7 more , Cheng CC, Tsai PS, Shih HC, Chen SC, Li CY, Ho TS, Syu GD
Virulence · 2026 Dec · PMID 41979069 · Full text
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its evolving variants, continues to challenge global efforts to control its spread....
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its evolving variants, continues to challenge global efforts to control its spread. Ongoing mutations may enhance transmissibility or lead to breakthrough infections, making immune monitoring crucial for public health policies. METHODS: A SARS-CoV-2 variant protein microarray was used to assess total and neutralizing antibodies against multiple variants. A serological survey was conducted in October 2022 in Tainan, Taiwan, including general citizens and special medical care groups. The general population comprised residents from the city (n = 504), suburban (n = 166), and country areas (n = 88). Special groups included individuals in elderly care centers (n = 50), nursing homes (n = 51), kidney dialysis patients (n = 100), and people living with human immunodeficiency virus (PLWH) (n = 45). Statistical analyses were performed using one-way and repeated-measures analysis of variance (ANOVA). RESULTS: The results demonstrated that the neutralization efficacy against Omicron and its subtypes declined according to the evolution of the variants, particularly in city and suburban areas. Special medical care populations, including individuals in elderly care centers, nursing homes, those undergoing kidney dialysis, and those PLWH, exhibited lower neutralization effectiveness. After analyzing the infection status, it can be found that special medical care populations had higher infection rates, especially in elderly care centers and nursing homes. CONCLUSIONS: SARS-CoV-2 protein microarray analysis is essential for assessing immunity at a population level. The findings highlight the need for adjusted vaccination strategies and ongoing surveillance of humoral immunity to address emerging SARS-CoV-2 variants effectively.
Divergent roles of OmpA family proteins in physiology, stress tolerance, and virulence of .
Liu F, He F, Gu Z … +1 more , Hu R
Virulence · 2026 Dec · PMID 41964441 · Full text
species are emerging opportunistic pathogens responsible for life-threatening nosocomial infections. Their intrinsic multidrug resistance severely limits effective antibiotic treatment, necessitating urgent development o...
species are emerging opportunistic pathogens responsible for life-threatening nosocomial infections. Their intrinsic multidrug resistance severely limits effective antibiotic treatment, necessitating urgent development of novel therapeutic strategies. Among potential targets, outer membrane protein A (OmpA) family proteins have drawn increasing interest. However, the functional roles of OmpA family proteins in remain entirely uncharacterized, leaving their potential as targeted therapeutics unresolved. In this study, we identified a group of putative OmpA family proteins in strain FL160902 and systematically investigated the contributions of five OmpA members to bacterial physiology and virulence. Targeted gene deletions revealed marked functional divergence among these paralogs. Specifically, OmpA-1 and OmpA-3 were identified as master virulence determinants; their deletion resulted in impaired serum resistance, reduced cell adhesion capacity, and diminished lethality. Their deletion also induced extensive physiological dysregulation, including enhanced biofilm formation, increased surface hydrophobicity, and heightened susceptibility to oxidative stress. In contrast, deletions of -2, -4, and -5 resulted only in partial attenuation of virulence traits and restricted changes to specific physiological phenotypes. Collectively, these findings establish a functional hierarchy within the OmpA proteins and position OmpA-1 and OmpA-3 as high-priority molecular targets for developing precision therapeutics against this life-threatening, multidrug-resistant pathogen.
High-throughput transposon sequencing identifies HprR as a key regulator of the LEE operon and virulence in O157:H7.
Liu M, Wu P, Luo T … +9 more , Li L, Wang Y, Qin J, Liu D, Li X, Xiang B, Niu Y, Wang L, Liu B
Virulence · 2026 Dec · PMID 41947494 · Full text
Enterohemorrhagic (EHEC) comprises a prominent group of extracellular human pathogens that specifically colonize the colonic epithelium, leading to severe gastrointestinal diseases and representing a significant global...
Enterohemorrhagic (EHEC) comprises a prominent group of extracellular human pathogens that specifically colonize the colonic epithelium, leading to severe gastrointestinal diseases and representing a significant global public health threat. During infection, EHEC O157:H7-the most prevalent serotype - tightly adheres to intestinal epithelial cells and induces the formation of characteristic attaching and effacing (A/E) lesions. However, the molecular mechanisms governing this close interaction remain incompletely understood. In this study, we employed transposon-directed insertion-site sequencing (TraDIS) to conduct a genome-wide screen for genes essential for EHEC O157:H7 adherence. Among the identified candidates, disruption of (encoding the response regulator of the HprS/HprR two-component system) resulted in markedly reduced epithelial colonization. Subsequent mechanistic analyses revealed that HprR positively regulates expression of genes within the locus of enterocyte effacement (LEE) pathogenicity island in a Ler-dependent manner, thereby promoting type III secretion system (T3SS) activity and epithelial colonization. Additionally, during luminal survival, HprR was found to directly bind to the promoter region of , a gene encoding a transthyretin-like protein, thereby enhancing bacterial resistance to oxidative stress and promoting persistence in the colonic lumen. Collectively, this study defines a comprehensive genomic framework for understanding EHEC O157:H7 colonization and identifies HprR as a dual-function regulatory protein that coordinates both epithelial adherence and luminal survival, thereby shaping host-pathogen interactions.
PRRSV subverts host programmed cell death network for immune evasion.
Ma S, Mao Q, Weng S … +4 more , Lian K, Jiang Z, Hao J, Zhang K
Virulence · 2026 Dec · PMID 41947476 · Full text
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen endangering the global swine industry, causing severe reproductive disorders in sows and respiratory diseases in piglets, and incurring subs...
Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen endangering the global swine industry, causing severe reproductive disorders in sows and respiratory diseases in piglets, and incurring substantial economic losses. This review summarizes how PRRSV interferes with multiple programmed cell death (PCD) modalities, including apoptosis, autophagy, pyroptosis, and ferroptosis, thereby optimizing its replication microenvironment, evading host immune responses, and establishing persistent infection. Furthermore, it details the spatiotemporal-specific strategies of PRRSV in regulating PCD during different infection stages and in various cell types, and highlights the pivotal role of virus-host protein interactions in viral pathogenesis. Collectively, this review systematically elucidates the molecular mechanisms by which PRRSV manipulates the host PCD network, and provides crucial theoretical guidance for PRRSV control research and antiviral drug development.
Bovine viral diarrhea virus vaccines: Current advancements, challenges, and future perspectives.
Pang F, Liang S, Zhou W
Virulence · 2026 Dec · PMID 41943428 · Publisher ↗
Bovine viral diarrhea virus (BVDV) represents a significant global threat to the cattle industry, incurring major economic liabilities. Vaccination remains the cornerstone of BVDV management. This review synthesizes the...
Bovine viral diarrhea virus (BVDV) represents a significant global threat to the cattle industry, incurring major economic liabilities. Vaccination remains the cornerstone of BVDV management. This review synthesizes the evolution of BVDV vaccine development, ranging from conventional inactivated (IV) and modified live virus (MLV) vaccines to next-generation platforms, including recombinant subunit, vector-based, nucleic acid-based, and virus-like particle (VLP) vaccines. We critically compare these approaches regarding their immune responses, cross-protective efficacy, safety, and ability to prevent fetal persistent infection (PI). Significant challenges persist, notably the high genetic and antigenic variability of BVDV, the reservoir of PI animals, and maternal antibody interference. In conclusion, we emphasize the need to prioritize research into novel vaccine platforms, advanced adjuvants, and multivalent or combination vaccines that cover diverse BVDV sub-genotypes and co-pathogens. These strategies are essential for generating the broadly protective, cost-effective vaccines required to support global eradication efforts.
effector GRA35 mediates neuronal damage ER stress and mitochondria-associated apoptosis.
Wang J, Chen Y, Zhou N … +7 more , Li F, Dai N, Chen Z, Liu S, An R, Chen L, Du J
Virulence · 2026 Dec · PMID 41940502 · Full text
Encephalitis resulting from acute reactivation of chronic infection in the central nervous system poses a significant mortality risk in immunodeficient individuals. However, the specific molecular mechanisms underlying...
Encephalitis resulting from acute reactivation of chronic infection in the central nervous system poses a significant mortality risk in immunodeficient individuals. However, the specific molecular mechanisms underlying this process remain elusive. We constructed the GRA35 gene knockout ME49 strain and compared the differences with wild type ME49 strain. We used the GST-pull down experiment to explore the mechanism of GRA35 promoting neuronal cell apoptosis. We used immunofluorescence, flow cytometry and CCK8 experiments to verify the pathway of GRA35 promoting neuronal cell apoptosis. Our study reveals that wild type ME49 strain promotes neuronal apoptosis in brain following chronic infection activation. Conversely, infection with the ME49 strain leads to a reduced apoptotic response in brain neurons. Furthermore, we demonstrate that GRA35 interacts with RTN1-c, thereby promoting mitochondrial pathway-mediated apoptosis in neurons. Additionally, GRA35 can trigger host cell ER stress-associated apoptosis through the PERK signaling pathway. GRA35 serves as a crucial virulence factor in the pathogenesis of Toxoplasmic encephalitis (TE), which offers potential new therapeutic target and theoretical insights for TE.
Wzi modulates immune evasion of hypervirulent in a CPS-dependent and independent manner.
Wei S, Xu T, Xiang Q … +9 more , Liu J, Li D, Zhang J, Huang L, Liu J, Liu J, Chen Y, Du Q, Zhou K
Virulence · 2026 Dec · PMID 41940501 · Full text
Hypervirulent (hvKP) poses a significant public health threat due to its ability to cause severe invasive infections with higher mortality than classical strains. Understanding its pathogenesis is essential for devising...
Hypervirulent (hvKP) poses a significant public health threat due to its ability to cause severe invasive infections with higher mortality than classical strains. Understanding its pathogenesis is essential for devising effective treatment strategies. We analyze shared virulence-associated genes from three hvKP transposon mutagenesis libraries and identify as a key virulence determinant of hvKP. We demonstrate that Wzi deficiency reduces CPS production in . , differing from its function as a CPS anchor in . Importantly, Wzi exerts a pivotal role in . pathogenicity through CPS-dependent and -independent mechanisms. It promotes hvKP survival in the host by suppressing IFN-γ-related cytokine secretion during early infection via CPS-dependent pathways. Wzi and CPS independently trigger sustained neutrophil recruitment through CXCL1 upregulation, resulting in pulmonary barrier damage and enhanced bacterial systemic dissemination for encapsulated . Wzi further enables to evade neutrophil-mediated clearance in a CPS-dependent manner. Notably, sequence polymorphisms significantly influenced serum resistance independent of CPS, with hvKP-associated alleles conferring the highest resistance. Our findings collectively highlight Wzi as a CPS-dependent and -independent virulence factor that mediates immune evasion and tissue invasion of hvKP, highlighting its potential as a therapeutic target for combatting hvKP infections.
Novel_circ_002651 regulates the immune defense of eastern honeybee larvae against fungal invasion through sponging miR-6001-y.
Zhang K, Wang F, Fan N … +8 more , Fan X, Wu T, Geng Y, Chen X, Qiu J, Fu Z, Chen D, Guo R
Virulence · 2026 Dec · PMID 41940497 · Full text
While high-throughput sequencing and bioinformatic predictions have identified numerous circRNAs in honeybees, research into their functional roles and molecular mechanisms remains limited. This study aims to characteriz...
While high-throughput sequencing and bioinformatic predictions have identified numerous circRNAs in honeybees, research into their functional roles and molecular mechanisms remains limited. This study aims to characterize the regulatory functions of a previously identified circRNA (novel_circ_002651, ac2651) and its key target miRNA (ace-miR-6001-y), in eastern honeybee worker larvae responding to infection by , a causative fungal pathogen for chalkbrood disease. Here, RT-qPCR detection showed that the expression of ac2651 was significantly down-regulated in the 6-d-old larval gut, while the ace-miR-6001-y expression exhibited an opposite trend. RNAi-based interference of ac2651 significantly increased the expression of both host immune genes and fungal proliferation-associated genes. Additionally, silencing ac2651 resulted in a reduction of host survival rate and a significant elevation of chalkbrood incidence. Overexpression and knockdown experiments demonstrated that ace-miR-6001-y negatively regulated the expression of in the larval guts and affected the expression of , , and in . Dual-luciferase reporter assay confirmed direct interactions between ac2651 and ace-miR-6001-y as well as between ace-miR-6001-y and . It was validated that simultaneous ac2651 silencing and ace-miR-6001-y knockdown reversed the upregulation of induced by ace-miR-6001-y knockdown alone. These results delineate a novel regulatory axis wherein ac2651 sponges ace-miR-6001-y to alleviate its repression of , thereby activating the host immune defense against the infection. Our findings not only offer novel insights into the interaction between honeybee larvae and fungal pathogen but also provide promising biomarkers and targets for the diagnosis and treatment of chalkbrood.
HosA-mediated epigenetic regulation of growth, virulence, and secondary metabolism in .
Zhou Z, Zhu Y, Gao R … +4 more , Wang Y, Chen Y, Lu L, Zhang Y
Virulence · 2026 Dec · PMID 41928566 · Full text
is a major opportunistic fungal pathogen whose pathogenic success relies on tight coordination between growth, metabolism, and environmental adaptation. Secondary metabolites (SMs) contribute to virulence and ecological...
is a major opportunistic fungal pathogen whose pathogenic success relies on tight coordination between growth, metabolism, and environmental adaptation. Secondary metabolites (SMs) contribute to virulence and ecological fitness but impose substantial metabolic costs. Here, we identify the histone deacetylase HosA as a chromatin-level regulator that promotes fungal growth and virulence while repressing secondary metabolism. Genome-wide ChIP-seq revealed no significant global changes in acetylation upon deletion but revealed locus-specific increases across the fumagillin/pseurotin supercluster and the Velvet complex genes. Transcriptomic analyses at 28°C and 37°C demonstrated temperature-dependent regulation of SM clusters that correlates with reduced expression at lower temperatures. Loss of HosA further enhanced fumagillin-dependent inhibition of Gram-positive bacteria, highlighting a trade-off between growth and chemical defense. Together, our findings uncover a chromatin-based regulatory mechanism that coordinates fungal growth, virulence, and secondary metabolism, providing insights into pathogenic fitness and potential antifungal target development.
Pathogenicity of Rift Valley fever virus: Organ-specific clinical outcomes and hidden drivers of virulence - a narrative review.
Nicole F, Legrand AF, Confort MP … +4 more , Ratinier M, Mathieu C, Lozach PY, Arnaud F
Virulence · 2026 Dec · PMID 41928558 · Full text
Rift Valley fever virus (RVFV) is a mosquito-borne phlebovirus posing major threats to human and animal health. Despite decades of research, the determinants governing diverse clinical manifestations remain incompletely...
Rift Valley fever virus (RVFV) is a mosquito-borne phlebovirus posing major threats to human and animal health. Despite decades of research, the determinants governing diverse clinical manifestations remain incompletely understood. This narrative review examines four central facets: i) exposure route impacts on disease outcome; ii) field strain diversity and organ-specific virulence; iii) genome reassortment driving viral evolution; and iv) organ-specific pathology including the overlooked placental/retinal infections. Differences among infection routes, viral strains, and host species complicate extrapolation from experimental models to outbreaks. Collectively, evidence indicates that RVFV pathogenesis results from interplay between infection route, viral determinants, and host factors including age and immune responses, which shape viral dissemination, tissue tropism, and organ-specific disease outcomes. Despite progress, major uncertainties remain regarding mechanisms controlling tissue tropism and field strain diversity roles in severe manifestations. Integrating field isolates, organotypic cultures, and physiologically relevant models will be essential to refine understanding and improve prevention.
Emergence of in the clinical high-risk clone sequence type 147 among carbapenem-resistant isolates in China: A multicentre retrospective study.
Wang C, Shen S, Gao X … +8 more , Huang X, Wang Y, Lv L, Yue C, Yu H, Sun Z, Liu JH, Hu F
Virulence · 2026 Dec · PMID 41923377 · Full text
The plasmid-mediated tigecycline resistance gene and its variants have emerged as a public health threat, with increasing identification in various sources of Enterobacterales worldwide. However, comprehensive epidemiol...
The plasmid-mediated tigecycline resistance gene and its variants have emerged as a public health threat, with increasing identification in various sources of Enterobacterales worldwide. However, comprehensive epidemiological features of in clinical carbapenem-resistant (CRKP) remain limited. Herein, we conducted a retrospective nationwide surveillance to assess the prevalence and molecular epidemiology of clinical -positive isolates from 4314 non-duplicated CRKP strains collected from 151 medical institutions across 31 provinces, municipalities, and autonomous regions in China. was detected in 18 (0.42%) CRKP strains spanning 12 provinces, all exhibiting multidrug resistance phenotypes. ST147 was the dominant sequence type and predominantly co-harbored . Phylogenetic analysis unveils the intrahospital, interhospital, and interprovincial spread of carrying ST147 CRKP, which display a closer genomic proximity to those from other global regions, suggesting the international transmission risk of . Variable tigecycline resistance levels among isogenic ST147 strains were associated with differential expression. Further, three types of plasmid replicons were found in the carriage of , among which IncFIB(K) and IncFIB(K)/IncHI1B were the primary vectors of , and a multireplicon megaplasmid was identified. The emergence of regionally disseminated -bearing ST147 CRKP clone highlights the potential global spread risk of , underscoring the urgent need for further surveillance and control measures to mitigate the ongoing spread of this resistant pathogen.
Monkeypox virus replication and host response in vaginal and ectocervical epithelial cells.
Mariotti D, Picarone L, D'Auria A … +13 more , Rosa L, Valeriani V, Pietrucci D, Meschi S, Carletti F, Mazzotta V, Antonelli G, Girardi E, Scagnolari C, Chillemi G, Antinori A, Maggi F, Matusali G
Virulence · 2026 Dec · PMID 41880196 · Full text
Recent mpox outbreaks have shown a predominant transmission through sexual contact. Replication-competent virus has been detected in seminal fluid, while in female patients, vaginal lesions, vertical transmission, and mi...
Recent mpox outbreaks have shown a predominant transmission through sexual contact. Replication-competent virus has been detected in seminal fluid, while in female patients, vaginal lesions, vertical transmission, and miscarriage risk have been reported. This study explored the susceptibility of the lower female genital tract (LFGT) to monkeypox virus (MPXV) infection, the role of sex-hormones in modulating viral replication, and host-virus molecular interactions. Human vaginal (VK2/E6E7) and ectocervical (Ect1/E6E7) epithelial cells were exposed to MPXV clade IIb, and viral replication was assessed. The influence of sex-hormones was evaluated after pretreatment with physiological concentrations of 17-β-estradiol or progesterone. Cellular genes' expression was determined by RT-qPCR and RNAseq, and ELISA was used for protein release analysis. Both cell lines supported productive MPXV infection. 17-β -estradiol and progesterone slightly reduced viral replication in Ect1/E6E7. At 48 hours post-infection, compared to uninfected control, 216 differentially expressed genes (DEGs) were identified in MPXV infected VK2/E6E7 and 11 in Ect1/E6E7, with nine shared DEGs involved in protein folding (HSPA6), chemotaxis (CXCL3, ARC), inflammation and lymphoproliferation (IL11, IL1RL1, MMP-1), and tissue remodeling (IGFN1, MMP-1). MPXV infection significantly increased MMP-1 release in both cell lines, and MMP-1 inhibitors reduced infectious virus production. IFN-β and IFN-λ1 were induced earlier and more pronouncedly in Ect1/E6E7 which also showed slower viral replication than VK2/E6E7. Our analysis demonstrated the MPXV-mediated modulation of common and tissue-specific cellular pathways in the LFGT. The perturbation of tissue remodeling and inflammation in this district has the potential to affect reproductive health and susceptibility to sexually-transmitted-infections.
Crosstalk between vimentin and keratins in viral infection: Implications across the viral life cycle.
Lu X, Wang X, Liu X … +1 more , Liu X
Virulence · 2026 Dec · PMID 41867121 · Full text
Intermediate filaments (IFs) have long been regarded as a static scaffold responsible for maintaining cellular structure and integrity. However, recent studies have revealed that IFs, particularly vimentin and keratin, e...
Intermediate filaments (IFs) have long been regarded as a static scaffold responsible for maintaining cellular structure and integrity. However, recent studies have revealed that IFs, particularly vimentin and keratin, exert a profound and versatile influence on viral infection. In this narrative review, we summarize how these IFs influence multiple stages of the viral life cycle, including attachment/entry, replication, intracellular trafficking, assembly, and egress. We further discuss their contributions to cell-to-cell spread, host immune regulation, and oncogenic processes. Collectively, these findings illustrate how viruses exploit or remodel the IF network to facilitate propagation, and highlight IF - virus interfaces as potential targets for antiviral intervention.
The complex subunit VdAP-2α regulates polar growth, ergosterol metabolism, and virulence in .
Wang YH, Zhu D, Wang D … +6 more , Sheng RC, Wang LC, Zhang CN, Latif MF, Li H, Chen FM
Virulence · 2026 Dec · PMID 41846537 · Full text
The normal polar growth and morphogenesis represent fundamental factors in development, reproduction survival and host invasion of phytopathogenic fungi. The heterotetramerized AP-2 complex is widely present in eukaryote...
The normal polar growth and morphogenesis represent fundamental factors in development, reproduction survival and host invasion of phytopathogenic fungi. The heterotetramerized AP-2 complex is widely present in eukaryotes and plays a specific role in clathrin-mediated vesicle formation and transport at the plasma membrane in mammals and plants. However, the functions of AP-2 complex in growth, metabolism and virulence of plant pathogenic fungi remain unclear. In this study, the conserved VdAP-2α subunit was identified in by screening of a T-DNA insertion library. was significantly induced during the developmental phases of , and its GFP-fused signals exhibited a punctate distribution in cytoplasm and on the plasma membrane. Like the insertional mutant, the deletion of caused the suppression of radial growth, conidiation and virulence, as well as aggravated formation of melanized microsclerotia. Comparative transcriptomic analysis further elucidated the global regulation of , including hyphal growth, vesicle transport, redox reactions and metabolic processes. Moreover, the impairment of hyphal polarity disordered chitin distribution, bidirectional conidia germination and hydrophobicity, which were associated with membrane defects caused by the decreasing of membrane-associated ergosterols and intermediates. These results contribute to the understanding of the functional characteristics of the AP-2 complex in filamentous fungi and suggest potential antifungal targets.
The bHLHzip-type transcription factor, , regulates conidial rodlet formation and cell surface hydrophobicity in the insect fungal pathogen .
Song D, Yan X, Xie S … +3 more , Guo G, Cao Y, Xia Y
Virulence · 2026 Dec · PMID 41843742 · Full text
Fungal conidial hydrophobicity plays critical roles in spore dispersal, host invasion, and environmental adaptation. However, the regulatory mechanisms underlying this phenomenon remain poorly understood. Here, we identi...
Fungal conidial hydrophobicity plays critical roles in spore dispersal, host invasion, and environmental adaptation. However, the regulatory mechanisms underlying this phenomenon remain poorly understood. Here, we identified , an uncharacterized bHLHzip-type transcription factor in the insect pathogenic fungus , and demonstrated its role in regulating conidial hydrophobicity along with other cellular processes. Deletion of resulted in reduced conidial yield, altered pigmentation, impaired stress tolerance, attenuated virulence, and decreased conidial hydrophobicity. Scanning electron microscopy revealed structural defects and surface alterations in Δ mutant conidia, including the reduction of the rodlet layer. Additionally, six hydrophobin encoding genes () were identified in the genome, and MaHpa3 was shown to act as a positive regulator of the expression of . Targeted deletion of phenocopied the hydrophobicity defect observed in the Δ mutant. Our findings establish MaHpa3 as a key regulator of conidial surface hydrophobicity and rodlet layer formation in .
Crystal structure of the effector SidL (Lpg0437) in complex with its metaeffector LegA11 (Lpg0436).
Machtens DA, Hutchison CA, Stein AM … +5 more , Eberhage J, Willerding JM, Eschenburg S, Shames SR, Reubold TF
Virulence · 2026 Dec · PMID 41843741 · Full text
is an opportunistic human pathogen that causes atypical pneumonia called Legionnaires' Disease. To replicate within host cells, injects up to 330 effector proteins into the host cytosol via a Dot/Icm type IV secretion s...
is an opportunistic human pathogen that causes atypical pneumonia called Legionnaires' Disease. To replicate within host cells, injects up to 330 effector proteins into the host cytosol via a Dot/Icm type IV secretion system. Several effectors, called metaeffectors, regulate the activity of other effectors within infected host cells through direct protein-protein interactions. LegA11 (AnkJ/Lpg0436) has been identified as a metaeffector of SidL (Ceg14/Lpg0437), one of eight effectors that inhibit host mRNA translation. LegA11 binds and suppresses SidL enzymatic activity, but the molecular basis of this regulation and impact on mRNA translation are unknown. Here, we present the crystal structure of SidL in complex with LegA11 to a resolution of 2.4 Å, revealing a high-affinity 1:1 complex with an extensive interaction interface of ~ 2300 Å. Using isothermal titration calorimetry, we determined a dissociation constant of 1.8 nM. translation assays demonstrate that SidL inhibits mRNA translation, and this activity is completely suppressed by LegA11. Mutagenesis of key interface residues in LegA11 disrupts complex formation and abolishes its metaeffector activity, confirming that LegA11 regulates SidL through direct protein-protein interaction. These findings show that LegA11 is a metaeffector that contributes to suppression of host mRNA translation by
Single-cell landscape of piglet lung response with .
Zhu J, Zhu S, Xia C … +13 more , Jiang X, Bao C, Li Z, Zhu R, Jiang H, Li F, Zhang X, Wang W, Chen H, Mei J, Gu J, Li N, Lei L
Virulence · 2026 Dec · PMID 41843736 · Full text
Pulmonary fibrosis is a prevalent, chronic, and fatal illness that poses considerable risks to life and health. () is an archetypal bacteria responsible for inducing significant pulmonary fibrosis, resulting in substant...
Pulmonary fibrosis is a prevalent, chronic, and fatal illness that poses considerable risks to life and health. () is an archetypal bacteria responsible for inducing significant pulmonary fibrosis, resulting in substantial economic losses in the pig industry. Nevertheless, the immune response in pig lungs against this pathogen and the specific characteristics of fibrosis remain obscure. In this study, single-cell RNA sequencing (scRNA-seq) analysis of piglet lungs with or without infection identified 18 subpopulations with different phenotypes. Monocytes, neutrophils, and plasmacytoid dendritic cells (pDCs) were enriched in the lungs post-infection and responded to infection by boosting IFN-γ-inducible and inflammatory-related gene expression. reduces the number of macrophages by inhibiting monocyte differentiation into interstitial macrophages (IM) and alveolar macrophages (AM) and triggering AM endogenous apoptosis. Furthermore, we identified significantly augmented pathological fibroblast-like cells that contributed to the rapid development of pulmonary fibrosis. In contrast, epithelial cells were significantly decreased and included those with features of epithelial-mesenchymal transition differentiated into fibroblasts through the signaling of TGFB1 and HIF1A. Cell-to-cell communication analysis further indicated that the interaction between the epithelial, vascular endothelial, pDCs, and fibroblast subsets, except for COL3A1 fibroblasts, was enhanced mainly via CD74/(COPA or MIF) receptor ligands after infection. Our findings elucidate the key pathogenic mechanisms driving bacterial pneumonia, while establishing a comprehensive molecular resource for developing targeted strategies against infection and related human fibrotic lung disorders.
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