Virulence最新文献

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.

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.

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.

Critical metabolic enzymes and pathways specific to bacterial adaptation in different host microenvironments directly contribute to bacterial pathogenicity. In this study, a virulent strain of the important zoonotic pathogen Streptococcus suis was found to show enhanced growth under anaerobic conditions compared to aerobic conditions. Transcriptomic analysis found a significant suppression of many central metabolic genes during anaerobic growth of S. suis. The transcriptomic data were used to reconstruct a genome-scale metabolic network to assess the distribution of metabolic fluxes in S. suis under different conditions. Significant activation of the arginine deiminase (ADI) and branched-chain amino acid (BCAA) biosynthesis pathways was identified. Gene deletion mutants of arcB and ilvC participating in these two pathways, respectively, were constructed. Compared to the wild-type strain, the ΔarcB mutant showed more significant growth deficiency under anaerobic conditions than under aerobic conditions. Accumulation of ATP and NH₃, the metabolites of the ADI pathway, was significantly higher when S. suis was cultured under anaerobic conditions, and this effect was attenuated in the ΔarcB mutant. The knockout of IlvC of the BCAA pathway disrupted the normal growth of S. suis in valine- and isoleucine-limited medium under anaerobic conditions. Both ΔarcB and ΔilvC showed attenuation in mice with decreased lethality, bacterial loads in tissues, and cytokine levels in serum, with the hypoxia-induced gene up-regulated in tissues. Therefore, ADI and BCAA pathways are critical for S. suis survival in response to hypoxia and infection in vivo, with ArcB and IlvC being promising drug targets.

Transfer messenger RNA (tmRNA), a key component of the trans-translation system, plays an essential role on the virulence of pathogenic bacteria. However, the upstream regulatory mechanisms that regulate tmRNA expression remain largely unexplored. In this study, AraC superfamily regulator (AsfR) was found to directly interact with the promoter of ssrA gene, which encodes tmRNA. Co-transformation of the reporter construct, consisting of tmRNA promoter fused to enhanced green fluorescent protein (eGFP), alongside an AsfR expression vector, resulted in increased fluorescence, indicating that AsfR positively regulates mRNA expression. Consistently, the transcription level of tmRNA was significantly decreased in ΔasfR compared with WT of A. veronii by quantitative real-time PCR (RT-qPCR) analyses. The ΔasfR and ΔtmRNA mutants exhibited significantly reduced motility and biofilm formation. Reduced transcription of the flagellar gene fliE in both mutants suggests that the AsfR/tmRNA axis may regulate these processes via fliE. Furthermore, deletion of asfR and tmRNA impairs oxidant resistance and pathogenicity, resulting in growth inhibition in A. veronii. This study elucidates the regulatory role of the AsfR-tmRNA pathway in flagellar motility, biofilm formation, and antioxidant capacity, all of which contribute to bacterial virulence and provide potential targets for the treatment of bacterial infections.

Peronophythora litchii is an oomycete pathogen responsible for litchi downy blight, a significant threat to global litchi production. Autophagy, a conserved degradation pathway crucial for the growth, development, and pathogenicity of phytopathogenic organisms, remains an area of active investigation. In this study, we characterized the function of the Atg26 homolog PlAtg26b in P. litchii. Using the CRISPR/Cas9 genome editing system, we generated PlATG26b knockout mutants and determined that PlAtg26b localizes to mitochondria under stress conditions. Although deletion of PlATG26b did not impair selective autophagy, it markedly reduced Atg8-PE synthesis, vegetative hyphal growth, asexual and sexual reproduction, and zoospore release. Furthermore, PlATG26b-deficient mutants exhibited significantly reduced virulence on litchi fruits and leaves. Collectively, our findings demonstrate that PlAtg26b plays a pivotal role in the biological development and pathogenicity of P. litchii.

Streptococcus suis is a major cause of sepsis and meningitis in pigs, and zoonosis through the emergence of disease-associated lineages. The ability of S. suis to adapt and survive in host environments, such as blood and cerebrospinal fluid (CSF), is important for pathogenesis. Here, we used Transposon Sequencing (Tn-seq) coupled with Nanopore sequencing to identify conditionally essential genes (CEGs) for the growth of S. suis P1/7 in active porcine serum (APS) and CSF derived from choroid plexus organoids. To our knowledge, this is the first successful application of ONT to Tn-library screening, enabling rapid local runs and a publicly available analysis pipeline. Through comparative fitness analyses, we identified 33 CEGs that support growth in APS and 25 CEGs in CSF. These genes highlight the importance of pathways related to amino acid transport, nucleotide metabolism, and cell envelope integrity. Notably, the LiaFSR regulatory system and multiple ABC transporters were important for proliferation. We also identified several genes of unknown function as essential for growth, pointing to previously unrecognized genetic factors involved in S. suis adaptation during infection. These findings provide new insights into the genetic requirements for S. suis survival in host-like environments and a deeper understanding of its ability to adapt to distinct physiological niches.

The diverse mycelial networks of fungi are generated through polar growth, cell division, and cell fusion. Most of the genes are well characterized as crucial for cellular communication and fusion processes in filamentous fungi, but their functions and molecular mechanisms remain poorly understood. Here, we functionally characterized the hyphal anastamosis protein 4 (AoHam4), hyphal anastamosis-8 protein (AoHam8) and serine/threonine protein phosphatase 2A (AoPP2A) in the model nematode-trapping fungus Arthrobotrys oligospora. Our results indicate that Aoham4, Aoham8 and Aopp2a genes are essential for hyphal fusion and trap morphogenesis, and modulate mycelial growth, conidial production, and pathogenicity in A. oligospora. Staining, RT-qPCR and transmission electron microscopy (TEM) results indicated that all three genes are involved in regulating reactive oxygen species (ROS) accumulation, lipid metabolism and autophagy processes. Moreover, RNA-Seq and liquid chromatography-mass spectrometry (LC-MS) experiments further confirmed that deletion of Aoham4, Aoham8 and Aopp2a genes affects transcription and metabolic levels. Yeast-two-hybrid (Y2H) analysis showed that AoPP2A can interact with AoSO (Soft, a fungus-specific scaffolding protein, is involved in signaling and secretion with the MAK-2 cascade). Since the ΔAoham8 mutant strain was more sensitive to cell wall-disrupting reagents, speculating that Aoham8 may regulate the mitogen-activated protein (MAP) kinase cascade response by activating the cell wall integrity pathway. Collectively, our studies illuminate the crucial roles of the fungal cell-fusion genes Aoham4, Aoham8 and Aopp2a in A. oligospora, as well as laying the groundwork for clarifying the mechanisms of mycelial development and trap morphogenesis of nematode-trapping fungi.

DDX17 (DEAD-box RNA helicase 17) is an essential RNA helicase and regulatory ATPase in host cells, extensively involved in various cellular processes during viral infections, such as RNA splicing, transcriptional regulation, and post-transcriptional modification. DDX17 exhibits dual functionality in viral infections: it enhances the stability, packaging, and replication of viral RNA through interactions with viral ribonucleoprotein complexes, as evidenced in infections caused by influenza viruses and Hantaan virus (HTNV). Conversely, DDX17 can inhibit viral proliferation by disrupting viral RNA metabolism, as observed in hepatitis B virus (HBV) and Epstein-Barr virus (EBV) infections, where it suppresses replication by modulating viral RNA decapping and degradation. The dual role of DDX17 provides novel insights into host-virus interactions while also highlighting its significant potential as an antiviral therapeutic target. These findings are expected to establish a theoretical foundation for related research and offer valuable references for developing novel antiviral strategies.