Virulence最新文献

Severe fever with thrombocytopenia syndrome (SFTS), caused by Dabie bandavirus (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 Gallus gallus, 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.

Actinobacillus pleuropneumoniae causes porcine infectious pleuropneumonia in pigs. We aimed to characterize the phenotypic and genomic features of three A. pleuropneumoniae 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 cps and cpx loci. The serovar 5 strain ZJNH2023 has a full set of ApxI genes, Apa1/Apa2, intact flp family genes related to Flp pilus assembly, and a full set tadABCD genes related to adherence, while strains ZJXS2022 and AH2022 carry ApxIII gene set, lack ApxIAC genes and Apa1/Apa2, and do not have intact flp family genes. Thus, we conclude that possession of the cytotoxic ApxI gene set and those involved in adhesion contributes to higher pathogenicity of the serovar 5 strain ZJNH2023. Distinct GIs and floR-containing plasmids in these strains might have been involved in multiple resistance and horizontal transfer of ARGs on the pig farms.

Swine viral infections continue to impose major economic and animal-health burdens worldwide, with pathogens such as porcine epidemic diarrhea virus (PEDV), African swine fever virus (ASFV), and porcine reproductive and respiratory syndrome virus (PRRSV) causing recurrent outbreaks. Autophagy and ubiquitination are central degradative pathways that act as double-edged swords, serving both host defense and viral exploitation. In this narrative review, we synthesize recent advances showing how these pathogens manipulate ubiquitin - autophagy circuits while host cells counteract through selective autophagy. We propose an autophagy - metabolism - immunity triad that positions autophagy as a hub linking infection, metabolic reprogramming, and immune evasion. This integrated framework moves beyond the traditional view of autophagy as strictly antiviral or pro-viral. Deciphering how viruses hijack ubiquitin - autophagy axes reveals actionable therapeutic targets and translational opportunities for antivirals, adjuvants, and metabolic interventions to reduce the burden of swine viral diseases.

Vibriosis is the most important public health threat from seafood consumption and marine recreation. Pathogenic Vibrio spp. employ virulence factors, including hemolysins and secretion systems, frequently detected in human cases, but virulence data in northern and southern sea otters (Enhydra lutris kenyoni and E. l. nereis, respectively) are limited despite their potential as marine bioindicators. Genomic epidemiology was used to characterize virulence factors of Vibrio spp. genomes (n = 570), including V. alginolyticus (n = 55), V. diabolicus (n = 52), non-O1/O139 V. cholerae (n = 163), and V. parahaemolyticus (n = 287) collected in North America (2000-2019). Virulence factors of V. parahaemolyticus were compared between isolation sources: bivalves, environment, humans, and southern and northern sea otters. Hemolysins (tdh, trh) and type III secretion system 2 (T3SS2) gene prevalences were lowest in environmental isolates, while tdh and T3SS2 gene prevalences were higher in human and northern sea otter isolates than those from southern sea otters. A hemolysin allele (trh1) was detected almost exclusively in human and sea otter isolates. Despite V. parahaemolyticus genomic diversity, detected genomic clusters were comprised of highly related and tdh⁺/trh⁺ genomes from nonenvironmental sources including humans and sea otters. Observed pathology in Vibrio spp. positive sea otters frequently included septicemia, enteritis, and moderate-to-severe melena. Co-occurrence of T3SS2 and T6SS1 in V. parahaemolyticus was associated with pathological findings and ampicillin-susceptible genotypes, suggesting a trade-off between virulence and antimicrobial resistance. Based on these findings, V. parahaemolyticus undergoes selection pressures resulting in apparent expansion, i.e. genomic clustering, of tdh⁺/trh⁺ virulent strains infecting humans and sea otters.

Traditional antifungal drugs used against Candida albicans have several drawbacks, including the emergence of drug-resistant strains. In addition, developing novel antifungal agents requires long-term research and design. Drug repurposing, identifying and utilizing previously unknown functions of known drugs, such as antifungal activity, may be a quick method for mining efficient alternatives. Otilonium bromide (OB), an FDA-approved drug, is a quaternary ammonium compound used as a therapeutic drug for irritable bowel syndrome. We previously reported the inhibitory effect of OB against the spore germination of Cryptococcus neoformans. In this study, we found that the antifungal activity of OB against C. albicans was 2 μg/mL for both minimum inhibitory and fungicidal concentrations. OB could destroy the cell membrane and prevent C. albicans from undergoing yeast-to-hyphae transition, thus interfering with biofilm formation. Additionally, the efficacy of OB was abolished when iron ions were provided, suggesting that iron homeostasis was associated with the inhibition mechanism of OB. Interestingly, a therapeutic assay showed that OB demonstrated limited efficacy in reducing C. albicans burden in a murine systemic infection model. In summary, repurposing OB against C. albicans may facilitate the design of new antifungal drugs, and chemical modification could enhance the efficacy of OB to be more specific to fungal pathogens.

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 Aphthovirus in the family Picornaviridae. FMDV's 3C protein is a nonstructural protein and, moreover, is a protease (3C^pro) that adopts a chymotrypsin-like fold and harbors a Cys-His-Asp catalytic triad. The 3C^pro 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^pro concerning its multiple characteristics, including nucleotide and protein sequences, crystal structures, enzymatic activities, anti-3C^pro 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^pro as a protease functioning in the course of viral propagation.

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.

LeuO, initially identified as a leucine regulator in Escherichia coli, has since been identified as a global regulator required for bacterial pathogenicity in a broad range of bacteria, including Salmonella, Shigella, and Vibrio. This study aimed to determine the regulatory role of LeuO in Salmonella pathogenicity island (SPI)-2, essential for the intracellular proliferation of Salmonella enterica serovar Typhimurium (S. 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 S. Typhimurium 14,028 and identified a distinctive 23-nucleotide motif with high similarity to that previously discovered in E. coli. Notably, multiple LeuO-binding sites were predicted within SPI-2, primarily adjacent to the ssrA and ssrB loci. In vitro binding assays verified the high binding affinity between LeuO and three specific motifs located at positions -35 to -12 (ssrA₁),+231 to + 254 (ssrA₂) near ssrA, and at positions -622 to -599 (ssrB₃) near ssrB, relative to their transcription start sites. Furthermore, LeuO overexpression abolished the transcription of lacZ fused to the ssrA promoter containing ssrA₁ and ssrA₂, suggesting the direct repression of ssrA via LeuO-binding. The absence of LeuO increased the intracellular survival of S. 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 Salmonella during systemic infection.

Microsporidia are opportunistic, obligate intracellular fungi capable of causing keratoconjunctivitis. Because the clinical manifestations of microsporidia keratoconjunctivitis are indistinguishable from those of other etiologies, and the organism is difficult to culture, its diagnosis is challenging. The transmission routes of microsporidia keratoconjunctivitis remain poorly defined, and zoonotic sources have long been suspected but rarely confirmed. Between September 2024 and October 2025, a total of 15 confirmed cases of microsporidia keratoconjunctivitis were identified at Peking University Third Hospital. The diagnosis was established based on Giemsa-stained corneal scrapings and/or metagenomic next-generation sequencing (mNGS) of conjunctival lavage samples. Among these 15 patients, microsporidia spores were observed in corneal scrapings from nine individuals, while 13 tested positive for Encephalitozoon hellem (E. hellem) by mNGS. Notably, all affected patients reported a history of parrot exposure. Self-reported parrot exposures included direct ocular contact (n = 3) and indirect contact (n = 12). Six patients reported that their parrots had exhibited ocular abnormalities and diarrhea before the onset of the patients' symptoms, and two patients stated that their parrots had died prior to their clinical presentation. Ocular and fecal samples from three parrots associated with four patients were collected, and all the parrots tested positive for E. hellem by mNGS. These findings provide both clinical and molecular evidence supporting pet parrots as a zoonotic source of microsporidia keratoconjunctivitis. This emerging zoonotic threat calls for greater clinical awareness and attention to animal exposure history during diagnosis.

As opportunistic intracellular pathogens, viruses rely on numerous sequential interactions between host and viral factors for their replication. Given the significance of molecular chaperones (heat shock protein 70 and heat shock protein 90) in mediating protein homeostasis, research has suggested that they are involved in viral infections in many ways. This study explored the roles of HSP70 and HSP90 in the Senecavirus A (SVA) life cycle. We demonstrate that HSP70 and HSP90 regulate virus internal ribosome entry site (IRES)-dependent translation activity by acting on SVA IRES. Additionally, we show that HSP70 promotes SVA IRES-dependent translation through association with SVA IRES domain II, and HSP90 may function through interaction with SVA IRES domain IV. Furthermore, we found that the structural proteins and four non-structural proteins (Lpro, 2B, 2C, 3A) were shown to interact with HSP70 and HSP90. Furthermore, we determined that HSP70 and Hsp90 activity is important for virus replication by stabilizing SVA proteins and preventing their degradation via the ubiquitin-proteasome, apoptosis, and autophagy-lysosome pathway. Our findings indicate that HSP70 and HSP90 activity is essential for SVA replication, offering new insights into the development of potential specific control strategies against SVA infection.