PLoS Pathogens最新文献

{"title":"Adaptive metabolic reprogramming of the brain tissue during late-stage Trypanosoma brucei infection maintains host learning and memory.","authors":"Nadin Fathallah, Chloe Barnes, Rebecca Chatwin, Jayde Whittingham-Dowd, John J Worthington, Lucy Jackson-Jones, Neil Dawson, Michael D Urbaniak","doi":"10.1371/journal.ppat.1014734","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014734","url":null,"abstract":"<p><p>Human African Trypanosomiasis (HAT) is a two-stage infection caused by Trypanosoma brucei ssp. In stage I the trypanosomes are in blood, lymph and tissue interstitial space and the infection progresses to stage II when the parasites enter the central nervous system (CNS), resulting in behavioural aberrations that proceed to coma and death. Here, we use a bioluminescent murine model of HAT to examine parasite localisation and the changes in host brain gene expression, metabolism and function, and behaviour that occur over the course of the infection. The murine HAT model reproduces the decrease in brain tryptophan well established in clinical samples, and we report for the first time an unprecedented 1.8-fold decrease in global brain glucose metabolism in stage II infection. These metabolic changes are accompanied by an 18-fold decrease in brain insulin transcripts without changes in pathways regulating the cellular responses to insulin. By contrast, genes involved in fatty acid and lipid metabolism are upregulated in the brain during stage II infection. Moreover, we show that transcriptional programmes regulating mitochondrial metabolism dynamically adapts across the time course of HAT infection, ultimately leading to a transcriptional programme that diverts host brain metabolism away from glycolysis during stage II infection. Overall, our data demonstrate a reprogramming of brain energy metabolism during stage II HAT infection that favours the utilization of fatty acids and lipids to meet the energy demands of the brain, with a reduced reliance on glucose metabolism. Despite the profound neurometabolic changes observed, host anxiety-like behaviour is unchanged and episodic learning and memory is not impaired, suggesting that brain metabolic reprogramming enables the utilisation of adipose reserves to maintain core brain functions. These finding may explain the progressive onset of neurological symptoms in HAT patients and inform the development therapeutic interventions to alleviate them.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 10","pages":"e1014734"},"PeriodicalIF":4.9,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149247126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral uracil treatment increases susceptibility to rectal SIV infection.","authors":"Elizabeth G Bodykevich, Fabiola Castello Casta, Jacob K Flynn, Charlotte A Nichols, Glenn A Nardone, Christine M Fennessey, Kelsie Brooks, Delmy Ruiz, Jennifer Simpson, Carol L Vinton, Brandon F Keele, Jason M Brenchley, Alexandra M Ortiz","doi":"10.1371/journal.ppat.1014716","DOIUrl":"10.1371/journal.ppat.1014716","url":null,"abstract":"<p><p>The intestinal microbiomes of men who have sex with men (MSM) are distinct as compared to non-MSM and may increase susceptibility to rectal HIV infection. We recently demonstrated that dysbiosis-associated disruptions to host antimicrobial immunity increase macaque susceptibility to rectal SIVmac239X acquisition. The described susceptibility-associated network identified Dual Oxidase 2 (DUOX2) - an epithelial sensor that catalyzes reactive oxygen species (ROS) production upon sensing pathobiont-derived uracil - as a likely contributor to increased SIV susceptibility. We hypothesized that intestinal, uracil bioavailability increases susceptibility to rectal HIV acquisition. Here, we treated rhesus macaques with oral uracil or uracil suppositories, prior to low-dose intra-rectal challenge with SIVmac239X. Oral treatment reduced pro-inflammatory cytokine production from peripheral T-cells but did not perturb rectal immunologic transcripts or epithelial ROS production and did not alter biomarkers of intestinal damage. Although treatment with uracil suppositories led to increased concentrations of fecal uracil and indices of intestinal damage, there were fewer immunological perturbations relative to oral treatment. Despite limited evidence of intestinal damage, oral uracil treatment increased susceptibility to intra-rectal SIV acquisition whereas uracil suppositories did not. These data provide mechanistic insights into intra-rectal SIV acquisition and may lead to novel therapeutic interventions that reduce incidence of HIV acquisition.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 10","pages":"e1014716"},"PeriodicalIF":4.9,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149247137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lyssavirus matrix protein stabilizes RGS4 to suppress ferroptosis via incomplete autophagy and iron metabolic reprogramming.","authors":"Jianqing Zhao, Pingping Chen, Meixin Sun, Chuan Liang, Zhen F Fu, Ling Zhao, Ming Zhou","doi":"10.1371/journal.ppat.1014726","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014726","url":null,"abstract":"<p><p>Rabies virus (RABV), the prototypical lyssavirus, suppresses neuronal ferroptosis through lipid droplet (LD) biogenesis, which is a critical immune evasion strategy we previously identified. However, the mechanistic link between LD formation and ferroptosis regulation during RABV infection remains poorly defined. Here, we report that RABV upregulate Regulator of G Protein Signaling 4 (RGS4), a ferroptosis-associated regulator, and this induction is strictly dependent on triglyceride synthesis and subsequent LD formation. Functionally, genetic or pharmacological inhibition of RGS4 elevates ferroptosis susceptibility, thereby restricting viral replication. Mechanistically, RGS4 depletion reduces HERC2, impairing the assembly of branched K48/K63 ubiquitin chains on NCOA4, which is essential for its proteasomal degradation, thereby enhancing NCOA4 stability. Stabilized NCOA4 promotes ferritinophagy, leading to degradation of ferritin heavy chain (FTH) and ultimately inducing ferroptosis. Critically, we identified that the lyssavirus matrix (M) protein directly counteracts this pathway: M protein inhibits RGS4 degradation via the Cys/N-degron system through incomplete autophagy, stabilizing RGS4 to maintain HERC2 expression, promote NCOA4 ubiquitination, and attenuate ferritinophagy. This mechanism reduces ferroptosis susceptibility and enables viral replication. Our findings unveil a novel lyssavirus-specific regulatory axis, RGS4-HERC2-NCOA4-FTH, that modulates ferroptosis, highlighting the critical role of ferroptosis in lyssavirus infection and pathogenesis.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 10","pages":"e1014726"},"PeriodicalIF":4.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wolbachia outcompetes mosquito-borne viruses by reprogramming host ATPSβ1-driven ATP metabolism toward symbiotic proliferation.","authors":"Hao Yuan, Yalan Zhang, Yaqi Zhao, Chaojun Wang, Yuanyuan Zhou, Qian Ni, Xiaodan Li, Bo Zhang, Yong Wang, Liang Cai, Hong Liu, Jinglin Wang, Juntao Gong, Meichun Zhang, Zhiyong Xi, Xiaoling Pan","doi":"10.1371/journal.ppat.1014692","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014692","url":null,"abstract":"<p><p>Wolbachia endosymbionts confer broad-spectrum resistance to mosquito-borne viruses. While the antiviral metabolites in Wolbachia-Aedes have been identified during viral replication, the core metabolic gene underlying this defense across the entire viral infection cycle remains undefined. Here, we demonstrated for the first time that Wolbachia strongly suppressed the emerging alphavirus Venezuelan equine encephalitis virus, extending its known antiviral spectrum. Transcriptomic and functional analyses revealed ATP synthase beta subunit 1 (ATPSβ1) as a key metabolic hub hijacked by both MBV and the symbiont. Without Wolbachia symbiosis, dengue virus and VEEV induced ATPSβ1 to promote viral binding via the viral envelope protein and increased intracellular ATP production for viral replication. Conversely, Wolbachia overrode ATPSβ1-mediated viral binding and redirected ATPSβ1-driven ATP synthesis to fuel its proliferation, strengthening antiviral activity. Pharmacologically, adenosine increased Wolbachia wAlbB density and potently suppressed viral infection in Ae. aegypti and Ae. albopictus cells. Oligomycin reduced intracellular ATP and inhibited viral infection in Wolbachia-free Ae. aegypti cells. Collectively, Wolbachia repurposes dual-functional ATPSβ1, which governs MBV binding and replication, into a potent antiviral effector through a metabolic tug-of-war over host ATP during symbiont-virus competition. Moreover, we highlight interventions targeting the ATPSβ1-driven metabolism as promising strategies to curb MBV transmission.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 10","pages":"e1014692"},"PeriodicalIF":4.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDIM drives the transition from repairable to catastrophic EsxA-mediated vacuole membrane damage during Mycobacterium marinum infection.","authors":"Céline Michard, Angélique Perret, Mélanie Foulon, Hendrik Koliwer-Brandl, Hubert Hilbi, Thierry Soldati","doi":"10.1371/journal.ppat.1014721","DOIUrl":"https://doi.org/10.1371/journal.ppat.1014721","url":null,"abstract":"<p><p>During infection, pathogenic mycobacteria damage the membrane of the Mycobacterium-containing vacuole (MCV), triggering host repair responses that preserve an intracellular permissive niche before bacteria escape to the cytosol at later stages. How the MCV transitions from repairable injury to catastrophic rupture remains poorly understood. Here, we dissected the respective contributions of the ESX-1 effectors EsxA/EsxB and the cell-envelope lipid phthiocerol dimycocerosate (PDIM) during Mycobacterium marinum infection of the amoeba Dictyostelium discoideum. Combining host reporters for membrane damage and repair with single and double bacteria mutants, we show that EsxA/EsxB and PDIM are both required for full intracellular virulence but act at distinct stages of MCV damage progression. Loss of EsxA/EsxB strongly reduced recruitment of ESCRT and autophagy reporters to the MCV, demonstrating that EsxA initiates repairable membrane lesions. In contrast, PDIM-deficient bacteria retained the ability to recruit early damage reporters and ESCRT machinery but showed reduced autophagy-associated repair, failed to efficiently acquire cytosolic perilipin coating, and remained largely confined within the MCV. Genetic disruption of host autophagy restored cytosolic access and increased intracellular growth of PDIM-deficient bacteria, indicating that PDIM is specifically required to overcome host repair capacity rather than to initiate damage. Importantly, the sequential requirement for EsxA and PDIM was conserved during infection of murine microglial BV-2 cells. Remarkably, PDIM-defective mutants induced lysenin recruitment, a reporter of sphingomyelin exposure, but progression to autophagy engagement was strongly decreased. Together, our results support a two-step model in which EsxA initiates MCV membrane damage, while PDIM amplifies these lesions towards catastrophic rupture, enabling escape to the cytosol and dissemination.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 10","pages":"e1014721"},"PeriodicalIF":4.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diverse infection models demonstrate robust resistance of Mycobacterium tuberculosis to innate immunity.","authors":"Marian R Fairgrieve, Ella C Brydon, Roberto A Chavez, Dmitri I Kotov, Russell E Vance","doi":"10.1371/journal.ppat.1014713","DOIUrl":"10.1371/journal.ppat.1014713","url":null,"abstract":"<p><p>Mycobacterium tuberculosis (Mtb) is a robust activator of innate immunity. While innate immune activation of macrophages can impact Mtb replication in vitro, there is little in vivo evidence that the innate immune system controls Mtb before the onset of adaptive immunity. Prior work has generally used specific pathogen-free (SPF) mouse models and relatively large infectious doses, which may obscure the capacity of innate immunity to control Mtb. Here, we performed ultra-low dose Mtb infections and found that the initial innate immune response was unable to curb even minimal Mtb infectious doses. Additionally, we primed the immune systems of C57BL/6 mice by co-housing with \"pet shop\" mice prior to Mtb exposure. Co-housed mice were as susceptible to Mtb infection as SPF mice. To pre-activate innate immunity at the site of Mtb infection more specifically, we also infected the lungs of mice with Legionella pneumophila (Lp) prior to Mtb. Innate immunity alone can clear large doses (>100,000 CFU) of Lp from the lung within a few days. However, priming the mouse lung by pre-infection with Lp only modestly reduced Mtb CFU compared to mice infected with only Mtb, indicating that Mtb can robustly replicate even in the presence of a strong anti-bacterial innate response. We performed single-cell RNA-sequencing on myeloid cells from mice either infected with Mtb alone or mice primed with Lp. We found that Lp priming before Mtb infection induced measurable changes in myeloid cells responding to Mtb, but these changes had little effect on innate control of Mtb. Together, these data demonstrate the robust resistance of Mtb to innate immune clearance under diverse experimental conditions.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 10","pages":"e1014713"},"PeriodicalIF":4.9,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149240078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective persistence of HIV-1-infected T cell clones can occur through immune reprogramming driven by defective, transcriptionally active proviruses.","authors":"Martin V Hamann, Lisa Brauckmann, Christoph Schwarz, Michael Spohn, Ramon Stoeck, Sabrina M Leddy, Julie Frouard, Maisha Adiba, Riekje Winzer, Fabian Hausmann, Sanamjeet Virdi, Adam Grundhoff, Cedric Feschotte, Daniel Sauter, Frauke Muecksch, Nadia R Roan, Eva Tolosa, Ulrike C Lange","doi":"10.1371/journal.ppat.1014618","DOIUrl":"10.1371/journal.ppat.1014618","url":null,"abstract":"<p><p>People living with HIV (PLWH) on antiretroviral therapy (ART) accumulate primarily defective proviral sequences in genomes of often clonally expanded CD4 + HIV-1 target cells. The majority of viral-derived DNA is transcriptionally active and preferentially found at distinct genomic loci suggesting a selective process driven by integration site-specific crosstalk between viral and host sequences. Focusing on one of the most prominent selected integration loci, the BTB Domain and CNC Homolog 2 (BACH2) gene, we here show mechanistic insights how CD4 + T cells are functionally reprogrammed via exaptation of provirus-derived regulatory sequences during long-term ART. Using a cellular model of BACH2-integrated proviruses, we find that proviral transcription drives aberrant BACH2 protein levels that escape autoregulatory feedback and impose BACH2-dependent transcriptomic changes. By mimicking these changes in primary CD4 + T lymphocytes, we observe that BACH2 drives reprogramming of cells toward a proliferative, precursor memory-like type. These reprogrammed CD4 + T cells possess traits of immune evasion and cellular survival that are signatures of persistent HIV reservoir cells in PLWH. Inhibition of provirus transcriptional activity can mitigate exaptation, suggesting a strategy to offset HIV-driven differentiation and expansion of CD4 + T cells. Finally, our data suggest that provirus exaptation at a second prominently selected proviral integration gene, the Signal Transducer And Activator of Transcription 5B (STAT5B) gene, drives a contrary, effector-like T cell fate, suggesting a multifaceted impact of exaptation on immune homeostasis. Overall, our data suggest that transcriptionally active proviruses, even if structurally defective, modulate target cells through insertional activation of integration genes, a process which we postulate to contribute to the complex immune modulation and dysregulation experienced by ART-suppressed PLWH.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 10","pages":"e1014618"},"PeriodicalIF":4.9,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13682663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Venom vesicles from the parasitoid Ganaspis hookeri facilitate venom protein entry into host immune cells.","authors":"Nicholas M Bretz, Chris Lark, Sarah Perkel, Rebecca Jackson, Jeremy D Driskell, James A Mobley, Nathan T Mortimer","doi":"10.1371/journal.ppat.1014707","DOIUrl":"10.1371/journal.ppat.1014707","url":null,"abstract":"<p><p>The parasitoid wasp Ganaspis hookeri infects Drosophila melanogaster larvae, laying an egg and injecting venom directly into the host body cavity. While infected hosts mount an immune response in an attempt to eliminate the parasitoid egg, parasitoid venom proteins act to inhibit these host responses and manipulate host physiology to ensure infection success. A key immune suppressive venom protein in G. hookeri is a venom-specific isoform of the SERCA (Sarco/endoplasmic reticulum calcium-ATPase) calcium pump. However, SERCA is a large hydrophobic protein, and the mechanism by which it and other venom proteins are transported into host cells is not well understood. Electron microscopy and nanoparticle tracking analysis of G. hookeri venom revealed the presence of venom extracellular vesicles (vEVs) as a putative transport mechanism. We characterized the biophysical properties of vEVs, and found that G. hookeri venom contains multiple vesicle types that are distinguishable by size, zeta potential, protein content, and density. A subset of these vEVs contain SERCA, and we found that fluorescently labeled vEVs are able to enter into host immune cells and alter host intracellular calcium levels, and that disruption of vesicle integrity results in the loss of this SERCA activity in host cells. Together, our data support a model in which G. hookeri venom proteins, including SERCA, are packaged into an array of venom vesicles, and are transported into host cells for immune suppression.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 10","pages":"e1014707"},"PeriodicalIF":4.9,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13693980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV-1 compartmentalization in the central nervous system during cryptococcal meningitis: Analysis of viral, fungal, and host factors.","authors":"Maura Manion, Camille M Lange, Ana M Ortega-Villa, Christine M Fennessey, Brandon F Keele, Matthew Moeser, Helene Highbarger, Kristi Huik, Natalie Lindo, Christian Gonsalves, James Virga, David B Meya, Sarah B Joseph, David R Boulware, Irini Sereti, Frank Maldarelli","doi":"10.1371/journal.ppat.1014697","DOIUrl":"10.1371/journal.ppat.1014697","url":null,"abstract":"<p><p>Opportunistic infections in the central nervous system (CNS), such as cryptococcal meningitis (CM) have profound consequences for people living with HIV-1 (PWH), including blood-brain barrier impairment and neuroinflammation. To investigate how CM may shape the HIV-1 populations in the CNS, we characterized viral variants in the blood and cerebrospinal fluid (CSF) compartments in PWH with active CM. Thirty-nine participants with CM had paired plasma and CSF viral load measurements prior to the start of anti-retroviral therapy (pre-ART), with overall significantly higher HIV-1 viral loads in plasma compared to the CSF. Among those with CSF pleocytosis, CSF viral loads were relatively higher and CCR5 coreceptor-utilizing HIV-1 were more frequently detected. To investigate whether these differences were due to sustained HIV-1 replication in the CNS that generated genetically distinct viral lineages in the CSF (i.e., viral compartmentalization), we characterized pre-ART HIV-1 env populations in a subgroup of eighteen PWH with CSF HIV-1 RNA levels > blood (N = 9) and CSF RNA levels < blood (N = 9). Compartmentalization between CSF and plasma viral populations was detected in participants from both groups and was associated with higher interleukin-2 (IL-2) levels in CSF. In some cases, HIV-1 populations in CSF were compartmentalized from plasma, were exclusively macrophage-tropic and reached levels exceeding 105 copies/ml CSF. In other cases, HIV-1 infected cells trafficking across the plasma and CSF compartments seemed the most likely source of virus in the CSF. Post-ART analysis in one participant demonstrated emergence of distinct HIV-1 populations. This study demonstrates that opportunistic infections may have diverse effects in shaping HIV-1 viral populations.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 10","pages":"e1014697"},"PeriodicalIF":4.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The pathogenicity factor of DNA virus interacts with Arabidopsis deubiquitinases UBP12/13 to promote viral infection.","authors":"Shun Li, Fangqin Yu, Yi Zhang, Siqi Liu, Hui-Wen Wu, Nam-Hai Chua, Shulin Deng","doi":"10.1371/journal.ppat.1014686","DOIUrl":"10.1371/journal.ppat.1014686","url":null,"abstract":"<p><p>Plant DNA viruses, such as Cauliflower mosaic virus (CaMV) and Cabbage leaf curl virus (CaLCuV), are devastating pathogens that cause substantial yield losses in crops worldwide. These viruses assemble their genomes into minichromosomes with host histones. Histone post-translational modifications (PTMs) are important for viral replication and host resistance. In this study, we demonstrate that the CaMV pathogenicity factor P6 interacts with Arabidopsis deubiquitinases UBP12 and UBP13, which are typically negative regulators of plant immunity. Using affinity purification-mass spectrometry (AP-MS), we identified UBP12/13 as prominent P6 interactors and confirmed their nuclear association. CaMV infection and P6 overexpression increased UBP12 abundance, suggesting the latter promotes viral infection. By contrast, ubp12/13 mutants exhibited enhanced resistance, characterized by reduced accumulation of viral DNA and transcripts. Chromatin immunoprecipitation (ChIP)-qPCR showed that the monoubiquitinated H2A (H2Aub) and H3K27me3 modifications on the CaMV 35S promoter, but not the 19S promoter, were significantly elevated in ubp12/13 mutants compared with wild-type plants. Furthermore, UBP12/13 are also targeted by AC2, a transcriptional activator from CaLCuV, indicating a conserved strategy among plant DNA viruses. Our findings support a working model in which viral pathogenicity factors hijack UBP12/13, which in turn may alter H2Aub homeostasis on viral minichromosomes to relieve epigenetic silencing and promote infection. Together, these findings point to a previously unrecognized route by which plant DNA viruses may influence host chromatin-associated pathways and identify UBP12/13 as potential targets for engineering virus-resistant crops.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"22 10","pages":"e1014686"},"PeriodicalIF":4.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149197350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}