Virulence[JOURNAL]
Sun
200 papers
Identification of fidelity-determined residues of Porcine reproductive and respiratory syndrome virus through structural alignment.
Gao X, Zhang J, Gao P … +6 more , Ge X, Zhang Y, Han J, Guo X, Zhou L, Yang H
Virulence · 2026 Dec · PMID 41649343 · Full text
Porcine reproductive and respiratory syndrome virus(PRRSV) is an economically important pathogen for global pork industry. As a positive-strand RNA virus, lacking exonuclease-mediated proofreading, its RNA-dependent RNA...
Porcine reproductive and respiratory syndrome virus(PRRSV) is an economically important pathogen for global pork industry. As a positive-strand RNA virus, lacking exonuclease-mediated proofreading, its RNA-dependent RNA polymerase (RdRP) domain within the nonstructural protein 9(nsp9) plays a vital role in maintaining replication accuracy. To identify the residues of PRRSV that regulates replication fidelity, its RdRP structure was predicted by using Alpha Fold 2 and aligned with the solved structure of coxsackievirus B3 (CVB3) RdRP. This comparison identified conserved residues in PRRSV RdRP that are potentially involved in fidelity. Using site-directed mutagenesis, nucleoside analog sensitivity tests, and next-generation sequencing(NGS), it was found that the nsp9 K541R mutation enhances fidelity, as increasing viral resistance to mutagens like ribavirin, 5-Fluorouracil(5-FU), and 5-Azacytidine(5-AZC), as well as generating lower rate of non-contiguous junctions. In contrast, mutations at other positions, including A394G, L396S, and R401A, reduced fidelity and elevated frequency of recombination and mutation accumulation. Structural modeling revealed that the highly conserved residue K336 is spatially adjacent to the key fidelity site K541 but situated on the opposite side of the RNA channel. We found that K336R exhibits a dissociated "resistance-high recombination" phenotype. The findings reveal the importance of specific residues in PRRSV RdRP for replication fidelity and provide insights into the potential for improving the stability and safety of live attenuated vaccines through targeted modifications. Furthermore, the study emphasizes the structural conservation of fidelity determinants across RNA viruses, despite low sequence similarity, which can offer a framework for identifying fidelity key sites in other viral RdRPs.
lipidome: The dynamics of uptake and secreted lipids.
Cabrera Díaz CE, Cala MP, Jiménez-Díaz E … +1 more , Celis Ramírez AM
Virulence · 2026 Dec · PMID 41627286 · Full text
plays a crucial role as part of the human skin's mycobiome. However, this yeast has been detected in other niches, such as the gut. Despite being commensal, the pathogenic link in several dermatological conditions, but r...
plays a crucial role as part of the human skin's mycobiome. However, this yeast has been detected in other niches, such as the gut. Despite being commensal, the pathogenic link in several dermatological conditions, but recently, chronic diseases such as cancer, Crohn's disease, and Parkinson's disease, among others, have been explored. Lipids can be involved in fungal pathogenesis, and this yeast is characterized by a significant lipid metabolic versatility, with a lack of the complex fatty acid synthase (FAS) required for the de novo synthesis of fatty acids, as it relies on lipase-releasing enzymes. Here, we assess lipid dynamics (lipids consumed vs. lipids secreted) using lipidomic analysis in the supernatant of mDixon media during two growth phases. 87 lipids within 17 classes of lipids were identified in three different lipid uptake-secretion patterns. Some lipids were characteristic, including the presence of glycochenodeoxycholic acid, glycerophospholipids (such as phosphocholine), cardiolipins, and sphingolipids (such as Cer-PI). Interestingly, sterols, bile acids, cholic acid and its derivates, some phosphocholines, fatty acyls, and cardiolipins were lipids consumed over time. The dynamic consumption of these lipids could presume an intriguing role in the metabolism of lipid processes in this yeast that could determine the interaction process and its pathogenic role.
T cell populations are negatively correlated with natural killer and macrophage cell populations in aspirate samples of peripheral lymphadenopathies.
Moos PJ, Carey AF, Joseph J … +7 more , Kialo S, Norrie J, Moyareke JM, Amof A, Nogua H, Lim AL, Barrows LR
Virulence · 2026 Dec · PMID 41606824 · Full text
We employed single-cell RNA sequencing (scRNA-seq) of fine needle aspirates (FNAs) to describe the cells and communication networks characterizing granulomatous lymph nodes of TB patients. We uniformly identified several...
We employed single-cell RNA sequencing (scRNA-seq) of fine needle aspirates (FNAs) to describe the cells and communication networks characterizing granulomatous lymph nodes of TB patients. We uniformly identified several cell types known to characterize granulomas. Overall, we found the T cell cluster to be the most abundant. Other cell clusters that were uniformly detected, but that varied in abundance amongst the individual patient samples, were the B cell, plasma cell and macrophage/dendritic and NK cell clusters. When we combined all our scRNA-seq data from our current 19 patients, we distinguished T, B, macrophage, dendritic and plasma cell subclusters. The sizes of these subclusters also varied dramatically amongst the individual patients. In comparing FNA composition we noted trends in which T cell populations were negatively correlated with NK cell populations and with macrophage/dendritic cell populations. In addition, we discovered that the scRNA-seq pipeline detects Mtb RNA transcripts and associates them with their host cell's transcriptome, thus identifying individual infected cells. The number of infected cells also varies in abundance amongst the patient samples. CellChat analysis identified predominating signaling pathways amongst the cells comprising the various granulomatous lymph nodes, identifying several pathways involved in immune cell maturation, migration and adhesion.
The interaction between CfAda3 and CfGcn5 impacts growth, development, and virulence of .
Chen Y, Wang Y, Luo J … +2 more , Li H, Zhang S
Virulence · 2026 Dec · PMID 41588863 · Full text
is an important economic woody oil plant in many Asian countries, and the anthracnose caused by is prevalent in its cultivation regions, causing significant losses annually. We previously found that CfGcn5-mediated H3 a...
is an important economic woody oil plant in many Asian countries, and the anthracnose caused by is prevalent in its cultivation regions, causing significant losses annually. We previously found that CfGcn5-mediated H3 acetylation governs virulence of . To further elucidate the regulatory mechanism of CfGcn5, we carried out mass spectrometry analysis for CfGcn5-interacting proteins and identified CfAda3 protein for functional analysis. We found that CfAda3 was mainly localized in nucleus and cooperated with CfGcn5 to acetylate H3K18 for global gene transcription. Targeted gene deletion revealed that CfAda3 is involved in growth and conidiation. Similar to Δ mutant, the Δ mutant is defective in conidial germination, appressorial formation, autophagy, and in the response to environmental stresses. These combined effects result in its non-virulence on . In addition, we provided evidence showing that both NLS region and ADA3 domain are required for the localization and function of CfAda3. Moreover, we indicated that the interaction with CfGcn5 is essential but not sufficient for the normal localization and full function of CfAda3. Taken together, our studies not only illustrate the prominent roles of CfAda3 in growth, development, and virulence but also highlight how CfAda3 functions together with CfGcn5 in .
Dissecting the evolutionary forces shaping codon usage bias in SFTSV from eastern China: Insights from a previously underrepresented region.
Wang Y, Wang Z, Kou Z … +2 more , Pang B, Wen H
Virulence · 2026 Dec · PMID 41571581 · Full text
Severe fever with thrombocytopenia syndrome (SFTS), caused by (SFTS virus, SFTSV), poses a growing public health concern in East Asia. Limited genomic data from Shandong Province have restricted understanding of viral e...
Severe fever with thrombocytopenia syndrome (SFTS), caused by (SFTS virus, SFTSV), poses a growing public health concern in East Asia. Limited genomic data from Shandong Province have restricted understanding of viral evolution, while codon usage bias, a key factor in viral fitness and host adaptation, remains uncharacterized. In this study, we analyzed codon usage patterns in SFTSV strains from Shandong using newly 152 sequenced samples and publicly available genomes. Phylogenetic analysis identified seven genotypes, with genotype A being dominant. Viral genomes showed higher adenine (A) and guanine (G) content and a tendency to use G or cytosine (C) at the third codon position. Relative synonymous codon usage analysis demonstrated gene-specific preferences for codons ending in G/C. Effective number of codons values indicated weak overall codon usage bias. Further analyses suggested that both mutation pressure and natural selection influence codon usage, with natural selection playing the dominant role (52.8-91.4%), particularly in the nucleoprotein (91.4%) and nonstructural genes (89.5%). Codon adaptation index analysis across 12 host species indicated stronger codon adaptation to humans and , implying higher viral replication efficiency in these hosts. Overall, codon usage bias is primarily driven by natural selection rather than mutation pressure. These findings improve understanding of SFTSV molecular evolution and may inform strategies for surveillance, vaccine design, and host-specific intervention.
Spatiotemporal distribution and molecular characteristics of porcine diarrhea-associated viruses detected in Chinese pigs.
Wang Z, Yang K, Li K … +9 more , Hu S, He S, Du J, Hou F, Pan X, Zhao Y, Bi M, Li T, Mo X
Virulence · 2026 Dec · PMID 41566660 · Full text
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 province...
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.
Multi-omics dissection of metabolic hijacking: Infectious bronchitis virus orchestrates lipid-centric replication through PPAR-TGF-β crosstalk.
Yan K, Wang X, Bo Z … +4 more , Zhang C, Guo M, Zhang X, Wu Y
Virulence · 2026 Dec · PMID 41566643 · Full text
Avian infectious bronchitis virus (IBV) belongs to the genus (family ), causes severe multi-system disease in chickens, inflicting major global economic losses. The molecular interplay between IBV and host metabolic net...
Avian infectious bronchitis virus (IBV) belongs to the genus (family ), causes severe multi-system disease in chickens, inflicting major global economic losses. The molecular interplay between IBV and host metabolic networks remains poorly understood. Through integrated transcriptomic, metabolomic, and lipidomic profiling of oviduct tissues from specific-pathogen-free (SPF) chickens infected with the IBV QXL strain, we demonstrate tripartite metabolic reprogramming: 1) redirected glucose flux through the pentose phosphate pathway (PPP) to fuel nucleotide synthesis, 2) rewired lipid metabolism to prioritize membrane biogenesis over fatty acid β-oxidation, and 3) orchestrated glycerophospholipid remodeling. This integrated analysis revealed a coordinated upregulation of fatty-acid biosynthesis genes and accumulation of specific glycerophospholipids and eicosanoids. Mechanistically, IBV co-opts the Warburg effect and PPP activation while uniquely suppressing fatty acid β-oxidation to channel fatty acids toward lipid droplets (LDs) biogenesis. Phosphatidylserine (PS) overproduction (e.g. 2.55-fold increase in PS(22:0/22:6)) and phospholipase A (PLA)-mediated lysophospholipids (Lyso-PLs) and eicosanoids generation (e.g. 7.09-fold increase in prostaglandin E (PGE)) emerged as critical regulators of membrane dynamics and inflammatory signaling. This process was centrally coordinated by the significant activation of peroxisome proliferator-activated receptor (PPAR) (e.g. 1.74-fold increase in ACSL1) and transforming growth factor-beta (TGF-β) (e.g. significant increase in p-SMAD2) signaling pathways, directly linking lipid remodeling to immunomodulation. Functionally, targeting acetyl-CoA carboxylase (ACC) or glucose-6-phosphate dehydrogenase (G6PD), alongside TGF-β pathway modulation, synergistically curtailed viral replication . Our findings delineate a critical PPAR-TGF-β cross-talk that governs lipid remodeling during infection and identify host metabolic nodes that are potentially targetable for antiviral intervention.
Genomic characterization of serovars 5, 8, and 15 strains from diseased pigs in eastern Chinese provinces.
Li Y, Chai W, Pan H … +4 more , Fang W, Feng H, Shu J, He Y
Virulence · 2026 Dec · PMID 41560560 · Full text
causes porcine infectious pleuropneumonia in pigs. We aimed to characterize the phenotypic and genomic features of three strains from clinical cases in eastern Chinese provinces. The serovar 5 strain ZJNH2023 was more p...
causes porcine infectious pleuropneumonia in pigs. We aimed to characterize the phenotypic and genomic features of three strains from clinical cases in eastern Chinese provinces. The serovar 5 strain ZJNH2023 was more pathogenic than strains AH2020 and ZJXS2022 in a murine model and was resistant to multiple antimicrobials. The core genome SNP (single nucleotide polymorphism) tree indicates that the three isolates are clustered with serovars 5, 8, and 15 strains of archived genomes. They harbor plasmids conferring resistance to florfenicol and are of substantial genome diversity, having more prophages, genomic islands (GIs), and antimicrobial resistance genes (ARGs) than the strains of corresponding serovars from other studies. The capsule-related gene clusters in strains AH2022 and ZJXS2022 are different from ZJNH2023 and contain an ISApl1 family transposase between the and loci. The serovar 5 strain ZJNH2023 has a full set of genes, /, intact family genes related to Flp pilus assembly, and a full set genes related to adherence, while strains ZJXS2022 and AH2022 carry gene set, lack genes and , and do not have intact family genes. Thus, we conclude that possession of the cytotoxic gene set and those involved in adhesion contributes to higher pathogenicity of the serovar 5 strain ZJNH2023. Distinct GIs and -containing plasmids in these strains might have been involved in multiple resistance and horizontal transfer of ARGs on the pig farms.
Exogenous indole promotes florfenicol tolerance in .
Zheng Y, Fu L, Cao Z … +6 more , Zhang T, Fei J, Jiang M, Zhou Y, Shi Z, Su Y
Virulence · 2026 Dec · PMID 41560554 · Full text
Bacterial metabolism is important for antibiotic resistance and tolerance. However, the impact of indole on bacterial metabolism and antibiotic efficacy has not been fully elucidated. In this study, we investigated the e...
Bacterial metabolism is important for antibiotic resistance and tolerance. However, the impact of indole on bacterial metabolism and antibiotic efficacy has not been fully elucidated. In this study, we investigated the effect and specific mechanism of exogenous indole on the antibiotic susceptibility of , a common pathogen in freshwater and marine fish farming. We found that exogenous indole promoted tolerance to the antibiotic florfenicol, and reprogrammed the metabolome. A total of 108 metabolites were detected, including 66 differential metabolites that regulate various metabolic pathways, such as the tricarboxylic acid (TCA) cycle and nucleotide metabolism. Exogenous indole disrupted the TCA cycle in by increasing the intracellular NADH contents and activating the respiratory chain to increase the reactive oxygen species levels, thereby increasing the intracellular Fe content to activate the Fenton reaction, which in turn promotes the oxidative stress response. Furthermore, indole inhibited antibiotic entry into the cell and activated efflux pumps to reduce the intracellular antibiotic content, ultimately promoting antibiotic tolerance. In vivo, exogenous indole compromised the ability of florfenicol to protect fish survival and eliminate pathogenic bacteria. These results shed light on the metabolic changes induced by indole and suggest future directions for addressing antibiotic tolerance and clinical infections of . in aquaculture. This study serves as a reminder of the adverse effects of combining antibiotics with metabolites in aquaculture.
Functional proteomic analysis reveals -mediated meropenem resistance and its reversal by galactose.
Li X, Wu JQ, Long XR … +2 more , Hu SB, Jiang M
Virulence · 2026 Dec · PMID 41560552 · Full text
Salmonella enteritidis is a globally prevalent zoonotic pathogen with a broad host range and high pathogenicity, ranking among the most common serotypes within the . The widespread and often indiscriminate use of antibio...
Salmonella enteritidis is a globally prevalent zoonotic pathogen with a broad host range and high pathogenicity, ranking among the most common serotypes within the . The widespread and often indiscriminate use of antibiotics has driven a continual rise in antimicrobial resistance among S. Enteritidis strains, posing a significant threat to public health. In this study, we employed a quantitative proteomics approach to investigate differential protein expression between meropenem-sensitive and -resistant S. Enteritidis strains. Bioinformatic analyses revealed significant downregulation of all the genes associated with the bacterial chemotaxis pathway in the resistant strain. To further explore the functional relevance of this pathway, we generated deletion mutants of 15 chemotaxis-related genes and assessed their susceptibility to meropenem. Notably, deletion of the gene was associated with increased resistance. Given the known role of in galactose transport, we hypothesized and subsequently confirmed that exogenous galactose supplementation enhances the bactericidal activity of meropenem against resistant strains. This synergistic effect was further validated in animal infection models. Collectively, these findings provide novel insights into the molecular basis of meropenem resistance in S. Enteritidis and highlight the potential of metabolic modulation as a strategy to restore antibiotic efficacy.
Successful cell culture isolation and experimental pathogenicity evaluation of porcine bocavirus G3.
Hu Y, Min J, Xu H … +11 more , Li L, Shi Y, Wu H, Zheng J, Fu N, Xu M, Sun J, Zhou Y, Chen J, Yang T, Sun W
Virulence · 2026 Dec · PMID 41560550 · Full text
Since its initial discovery in Swedish pigs in 2009, porcine bocavirus (PBoV) has been detected across Asia, Europe, Africa, and North America. However, the pathogenic potential of PBoV has remained uncertain due to the...
Since its initial discovery in Swedish pigs in 2009, porcine bocavirus (PBoV) has been detected across Asia, Europe, Africa, and North America. However, the pathogenic potential of PBoV has remained uncertain due to the lack of suitable cell culture systems for viral propagation. In this study, we report the first successful isolation of a Chinese PBoV strain (BK19) from diarrheic piglets in Hunan Province using trypsin-supplemented LLC-PK1 cells. The isolate was characterized through immunofluorescence assay, electron microscopy, plaque formation, and growth kinetics. Whole genome sequencing revealed 43.4-95.7% nucleotide identity with known PBoV strains, with phylogenetic analysis classifying BK19 within the G3 genogroup. Experimental infection of 5-8, 17-19, and 31-33 days old piglets demonstrated age-dependent pathogenicity, with all groups developing characteristic clinical signs including fever, respiratory distress, and diarrhea lasting 3-4 days. Viral shedding peaked in rectal swabs at 4 days post-infection (dpi), with persistent detection through 14 dpi in 5-8 and 17-19 days old groups. Postmortem examination revealed broad tissue tropism in 5-8 and 17-19 days old piglets and age-dependent pathological lesions in intestinal, pulmonary, lymphoid and renal tissues. Immunohistochemical analyses confirmed viral antigen presence in these tissues in 5-8 days old piglets, which correlated with enhanced proliferation of infected cells. These findings provide definitive evidence that PBoV is a primary pathogen in swine, with particular clinical significance for young piglets. This study establishes crucial tools for further research into PBoV biology and control strategies.
Pangenomic analysis reveals metabolic adaptation of to the urogenital tract.
Davina-Nunez C, Rincon-Quintero A, Potel C … +5 more , Menéndez Rodríguez C, Montaño Barrientos BJ, Fontan-Silva B, Quintela-Baluja M, Perez-Castro S
Virulence · 2026 Dec · PMID 41518235 · Full text
(Hpar) is a common colonizer found in the upper respiratory tract, although recently urogenital colonization has emerged as a clinical concern. Urogenital Hpar has been associated with increased antibiotic resistance and...
(Hpar) is a common colonizer found in the upper respiratory tract, although recently urogenital colonization has emerged as a clinical concern. Urogenital Hpar has been associated with increased antibiotic resistance and virulence compared to respiratory Hpar. We analyzed the genome of 270 Hpar isolates, including all sequencing data found in the NCBI sequence read archive database. The pangenome of respiratory and urogenital isolates were compared in order to find potential metabolic or pathogenic adaptations to different host environments. The pangenome-wide association study found significant genomic differences. Specifically, the two-component signal transduction system was significantly enriched in urogenital samples, which could explain the adaptations of Hpar to the unique physico-chemical conditions of the urethra. Additionally, the two-component system could work as a new target for antimicrobials against pathogenic Hpar. The polysaccharide capsule, the main virulence factor in was present in 26/65 of the urogenital samples from our facility, an increase from previous studies. In summary, the data presented suggest that respiratory and urogenital isolates of Hpar belong to different genetic lineages, and therefore it is possible that unprotected oral sex is not the route of transmission of Hpar from the respiratory tract to the urethra. Given the limited amount of available sequences, future studies collecting more isolates from different spatiotemporal locations would shed more light on this issue.
Genomic profile of extraintestinal pathogenic isolates from prosthetic joint infections: The search for molecular fingerprints.
Meléndez-Carmona MÁ, Martín-Higuera MC, Recio R … +6 more , Benavent E, Gómez-Junyent J, Mancheño-Losa M, Hernández-Jiménez P, Chaves F, Lora-Tamayo J
Virulence · 2026 Dec · PMID 41518232 · Full text
is a key pathogen in extraintestinal infections, including prosthetic joint infections (PJIs), which account for approximately 9% of all such cases. Despite its clinical relevance, the molecular pathogenesis of in PJIs...
is a key pathogen in extraintestinal infections, including prosthetic joint infections (PJIs), which account for approximately 9% of all such cases. Despite its clinical relevance, the molecular pathogenesis of in PJIs remains poorly defined. This study investigated the clinical, phylogenetic, and virulence profiles of isolates from PJIs and compared them to isolates from bacteremic urinary tract infections (UTIs). A total of 13 isolates from each infection type were analyzed using whole-genome sequencing (WGS) to determine phylogenetic relationships, sequence types, and the presence of virulence genes. PJI isolates exhibited substantial genetic diversity, encompassing 10 sequence types, with ST131 and ST69 being the most frequent. Phylogroup B2 predominated (53.9%) among PJI isolates. Adhesion and biofilm-related genes, such as , , and , were highly prevalent in PJI isolates, supporting the role of biofilm formation in pathogenesis. Conversely, toxin-associated genes (e.g. and ) were more frequently detected in UTI isolates. Notably, the gene, linked to biofilm enhancement, was significantly associated with microbiological failure in PJIs (75% vs. 0%, = 0.02). Phylogenetic analyses revealed no clustering by infection type, suggesting that ExPEC strains share a versatile genomic background, enabling them to adapt to different infection environments. The study highlights the critical role of biofilm formation in PJIs and underscores the genetic adaptability of ExPEC strains, which lack distinct virulence profiles specific to PJIs. However, the small number of PJI isolates limits the generalizability of these findings and warrants confirmation in larger cohorts.
Virulence and transmission characteristic of H3N8 avian influenza virus circulating in chickens in China.
Mei M, Zhang X, Wu Q … +2 more , Xu M, Zhao Y
Virulence · 2026 Dec · PMID 41504338 · Full text
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...
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: 10· TCID/mL). ZJ07 demonstrated exceptional thermostability (HA activity persisting >3 hr at 56°C), while JS13 showed 1.8-fold elevated neuraminidase activity versus controls ( < 0.05). , 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 essential role of heparan sulfate in the entry of PDCoV and other porcine coronaviruses.
Ma N, Zhang M, Ghonaim AH … +9 more , Zhou P, Wang C, Zhou J, Guo G, Lebbink RJ, Bosch BJ, Zhu H, Li W, He Q
Virulence · 2026 Dec · PMID 41503690 · Full text
Porcine enteric coronaviruses, including porcine deltacoronavirus (PDCoV), porcine epidemic diarrhea virus (PEDV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and transmissible gastroenteritis coronavirus (TGEV...
Porcine enteric coronaviruses, including porcine deltacoronavirus (PDCoV), porcine epidemic diarrhea virus (PEDV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and transmissible gastroenteritis coronavirus (TGEV), can cause acute diarrhea, vomiting, dehydration, and high mortality in suckling piglets. Recent studies revealing human PDCoV infections and the potential of SADS-CoV to penetrate human cell lines have heightened apprehensions about the zoonotic transmission risks of these viruses. While heparan sulfate (HS) serves as a receptor in PDCoV binding, the key host genes involved in HS biogenesis and the specific molecular mechanisms underlying this process have not been fully examined. Enzymes involved in HS biosynthesis, including SLC35B2, EXT1, and NDST1, were identified as critical host factors via the use of CRISPR-Cas9 knockout cells. Moreover, inhibition assays using heparin sodium, a competitive HS mimic, demonstrated dose-dependent reductions in PDCoV infection . Additionally, mitoxantrone, an HS-binding drug, reduced PDCoV infection. Furthermore, HS was confirmed to facilitate the entry of other porcine enteric coronaviruses (SeCoVs), including PEDV, SADS-CoV, and TGEV, underscoring the conserved role of HS in CoV pathogenesis. These insights contribute to the understanding of porcine coronavirus-host interactions and support the development of innovative antiviral interventions.
Giardiavirus rewires host translation and glycolytic metabolism to support its replication in .
Li L, Cao L, Zhong C … +10 more , Zhang N, Li X, Wang X, Guo Y, Yu Y, Li J, Zhang X, Le Y, Yuan J, Gong P
Virulence · 2026 Dec · PMID 41445118 · Full text
is an intestinal protozoan parasite responsible for giardiasis, a disease primarily characterized by diarrhea and associated with long-term complications such as malnutrition and growth impairment in children. The presen...
is an intestinal protozoan parasite responsible for giardiasis, a disease primarily characterized by diarrhea and associated with long-term complications such as malnutrition and growth impairment in children. The presence of Giardiavirus (GLV) has been shown to attenuate pathological damage in -infected murine models and modulate distinct pro-inflammatory responses in host cells stimulated by . However, the understanding of the impact of the GLV on the itself remains limited. Here, we found that GLV infection interfered with the host protein expression system by reducing both mRNA and protein levels of genes, while paradoxically enhancing mRNA translation efficiency. Additionally, GLV infection induced energy metabolic reprogramming in , as evidenced by the identification of 21 significantly altered energy metabolites. KEGG enrichment analysis revealed glycolysis/gluconeogenesis as the most prominently enriched metabolic pathway in GLV-infected . Notably, glycolysis continued to be upregulated with successive passages of GLV infection, even after the GLV load plateaued. The glycolytic enzyme enolase was found to be closely associated with GLV infection within , and morpholino-mediated knockdown of enolase expression resulted in a significant reduction in GLV replication. Overall, these findings demonstrate that GLV infection manipulates host translation and energy metabolic pathways to facilitate its persistence in , and reveal both GLV and host metabolic targets as promising research subjects for developing drugs and vaccines for the prevention and treatment of giardiasis.
Foot-and-mouth disease virus 3C protease as virulence determinant plays multiple roles in cleaving viral polyprotein and host factors.
Zhou H, Wang M, Xin Z … +4 more , Li Z, Wang Q, Li Y, Liu F
Virulence · 2026 Dec · PMID 41442432 · Full text
Foot-and-mouth disease virus (FMDV) can cause a severe infectious disease that primarily affects even-toed ungulates. FMDV is classified into the genus of in the family . FMDV's 3C protein is a nonstructural protein and...
Foot-and-mouth disease virus (FMDV) can cause a severe infectious disease that primarily affects even-toed ungulates. FMDV is classified into the genus of in the family . FMDV's 3C protein is a nonstructural protein and, moreover, is a protease (3C) that adopts a chymotrypsin-like fold and harbors a Cys-His-Asp catalytic triad. The 3C plays crucial roles not only in cleaving the FMDV polyprotein but also in degrading various host proteins. Cleavage of the polyprotein contributes to generating different viral polypeptides. Degradation of host proteins possibly affects cellular signaling pathways, making FMDV impair innate immune responses. Here, we systematically reviewed FMDV 3C concerning its multiple characteristics, including nucleotide and protein sequences, crystal structures, enzymatic activities, anti-3C inhibitors, and more importantly, its functions in cleaving the viral polyprotein and host proteins. This review aims to provide a comprehensive insight into FMDV 3C as a protease functioning in the course of viral propagation.
The pathogenicity and virulence of Sindbis virus.
Sokoloski KJ, Karki D, Isom CM … +1 more , Moni S
Virulence · 2026 Dec · PMID 41442410 · Full text
Sindbis virus (SINV), a widely distributed alphavirus, is both a foundational model for viral replication studies and an underrecognized human pathogen. Despite its typically mild presentation, SINV can lead to prolonged...
Sindbis virus (SINV), a widely distributed alphavirus, is both a foundational model for viral replication studies and an underrecognized human pathogen. Despite its typically mild presentation, SINV can lead to prolonged joint pain and, in rare cases, neurological complications. This review explores SINV's molecular biology and clinical manifestations, particularly its role in causing Sindbis Fever - a self-limiting but potentially chronic arthritic disease. Molecular insights reveal mechanisms of immune evasion, neurovirulence, and persistent infection, highlighting SINV's potential for broader public health impact, especially under changing climatic conditions. This review also identifies key virulence determinants and discusses the virus's utility as a model for studying alphaviral encephalitis. Continued research is essential to better understand SINV pathogenesis and to prepare for potential outbreaks.
Metabolic control of macrophages in coronavirus disease 2019.
An L, Xu H, Fan Q … +2 more , Lu M, Sun D
Virulence · 2026 Dec · PMID 41437518 · Full text
In the context of COVID-19, macrophages are primarily responsible for sensing and responding to the virus, significantly influencing disease outcomes. They are involved in early pathogen recognition, immune activation, a...
In the context of COVID-19, macrophages are primarily responsible for sensing and responding to the virus, significantly influencing disease outcomes. They are involved in early pathogen recognition, immune activation, and tissue repair. Heterogeneity and phenotypic plasticity of macrophages are dynamically shaped by microenvironmental cues, including metabolites, hypoxia, and pathogen-derived signals. Notably, emerging evidence underscores that cellular metabolism, particularly in macrophages, dictates immune responses to viral infection. This metabolic-immune crosstalk critically determines COVID-19 severity, ranging from viral clearance to hyperinflammation or fibrosis. In this review, we systematically dissect how cell-intrinsic metabolic nodes and extrinsic factors modulate macrophage effector functions, while illustrating the complications associated with macrophage metabolic dysregulation in SARS-CoV-2 infection. These mechanistic insights provide a rational foundation for therapeutic strategies targeting macrophage metabolism to rebalance immune responses and mitigate COVID-19 complications.
Inhibitors of GapN-dependent NADPH supply as potential lead compounds for novel therapeutics against .
Schütt I, Einwohlt P, Wandinger AM … +11 more , Teuffel J, Wirsing R, Hlawatschke BH, Fehlauer HL, Bothe S, Bader N, Monaci E, Kreikemeyer B, Schindelin H, Wade RC, Fiedler T
Virulence · 2026 Dec · PMID 41437515 · Full text
Infections with are among the most important diseases caused by bacteria and are responsible for around 500,000 deaths every year. In 2024, macrolide-resistant was added to the WHO's list of priority pathogens. The non...
Infections with are among the most important diseases caused by bacteria and are responsible for around 500,000 deaths every year. In 2024, macrolide-resistant was added to the WHO's list of priority pathogens. The non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase GapN has been identified as a potential drug target in . SpyGapN is the major NADP-reducing enzyme in these bacteria as they lack the oxidative part of the pentose phosphate pathway. In this study, docking of compound libraries to the glyceraldehyde 3-phosphate binding pocket of SpyGapN was used to screen for potential competitive inhibitors. Among the candidates identified with this approach, 1,2-dihydroxyethane-1,2-disulfonate (glyoxal bisulfite) showed the strongest inhibition of SpyGapN activity . In a complementary approach, crystallographic fragment screening was conducted, which identified the ultra-low-molecular-weight compounds pyrimidine-5-amine and 4-hydroxypyridazine targeting the cofactor-binding pocket of SpyGapN. Both low-molecular-weight compounds were experimentally confirmed to inhibit the activity of purified SpyGapN. Combinations of glyoxal bisulfite with either pyrimidine-5-amine or 4-hydroxypyridazine enhanced the inhibitory effect of SpyGapN. Glyoxal bisulfite was able to kill . This effect was accelerated by combining glyoxal bisulfite with 4-hydroxypyridazine. While these findings suggest that inhibition of SpyGapN probably contributes to the observed antibacterial activity, the exact mechanism of action remains to be confirmed, as the compounds also affect other G3P-converting enzymes. Nevertheless, these compounds provide a promising starting point for the development of more specific SpyGapN inhibitors.
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