Molecular immunology最新文献

{"title":"TNF-α and IFN-γ modulate the evasion of the immune response in primary mediastinal B-cell lymphoma.","authors":"Paula Gršković, Valentino Mihalić, Anja Krstulović, Peter Möller, Suzana Hančić, Slavko Gašparov, Petra Korać","doi":"10.1016/j.molimm.2025.09.009","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.09.009","url":null,"abstract":"<p><strong>Objectives: </strong>Primary mediastinal B-cell lymphoma (PMBCL) is an aggressive type of non-Hodgkin lymphoma (NHL) that shares features with diffuse large B-cell lymphoma (DLBCL), but also with classical Hodgkin lymphoma (cHL). PMBCL often contains aberrations of genes involved in the immune response such as cREL and PD-L1, whose expression is also influenced by cytokines TNF-α and IFN-γ.</p><p><strong>Methods: </strong>In this study, cell lines Farage, U2940, MedB-1 and Karpas1106p were used as PMBCL models and treated with different concentrations of TNF-α and IFN-γ over 24 and 48 h, followed by the quantification of cREL, CXCL10 and PD-L1 expression. Additionally, the expression of TNF-α, IFN-γ, cREL, CXCL10, CXCR3, PD-L1 and PD-1 genes was compared between PMBCL tissue samples and B-cell and T-cell rich zones of non-tumour tonsils.</p><p><strong>Results: </strong>Prolonged exposure to TNF-α increased cREL expression, while IFN-γ strongly induced CXCL10 expression. The change in the expression of PD-L1 in response to the treatments differed across various cell lines. There was no statistically significant difference in the expression of the target genes between tumour and non-tumour patient tissue samples.</p><p><strong>Conclusions: </strong>the obtained results suggest that the immune checkpoints in PMBCL cells are affected by both their genetic profile and tumour microenvironment.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"178-187"},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S1PR2-miR-212 feedback loop regulates allergic reactions.","authors":"Jaewhoon Jeoung, Hyein Jo, Wonho Kim, Dooil Jeoung","doi":"10.1016/j.molimm.2025.10.001","DOIUrl":"https://doi.org/10.1016/j.molimm.2025.10.001","url":null,"abstract":"<p><p>We previously reported the anti-allergic effect of rocaglamide-A (roc-A). Molecular docking analysis showed the binding of roc-A to sphingosine-1-phospahe receptor 2 (S1PR2). This led us to hypothesize that S1PR2 might play a role in allergic reactions. Antigen stimulation increased the expression of S1PR2 in rat basophilic leukemia (RBL2H3 cells). Sphingosine-1-phosphate (S1P) increased the expression of S1PR2 in an antigen-independent manner. S1PR2 was necessary for both allergic reactions in vitro and anaphylaxis. Sphingosine prevented the antigen (DNP-HSA) from increasing the expression of S1PR2 and hallmarks of allergic reactions in RBL2H3 cells. Sphingosine also prevented antigen from increasing the level of reactive oxygen species (ROS). Animal model of passive systemic anaphylaxis (PSA) showed the increased expression of CXCL1. CXCL1 was shown to mediate allergic reactions in vitro. TargetScan predicted the binding of miR-212 to the 3 ´ UTR of S1PR2. The downregulation of S1PR2 prevented antigen from increasing the expression of CXCL1 at the transcriptional level. cmiR-212 was found to decrease the expression of S1PR2 in antigen stimulated RBL2H3 cells. miR-212 mimic decreased the luciferase activity associated with 3 ´ UTR of S1PR2. The miR-212 mimic exerted a negative effect on the passive cutaneous anaphylaxis (PCA). The downregulation of S1PR2 increased the expression of miR-212 in antigen stimulated RBL2H3 cells. This suggests that miR-212 and S1PR2 form negative feedback loops to regulate allergic reactions. Our results show that S1PR2-miR-212 negative feedback loop regulates allergic reactions in vitro and in vivo.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"166-177"},"PeriodicalIF":3.0,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145244814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PCBP2 alleviates myocardial infarction by inhibiting cardiomyocyte ferroptosis via the NDUFS1/NRF2 pathway.","authors":"Qianrong Zhang, Aiping Jin, Haijuan Cheng, Yuanyuan Zheng, Bing Li","doi":"10.1016/j.molimm.2025.08.002","DOIUrl":"10.1016/j.molimm.2025.08.002","url":null,"abstract":"<p><strong>Background: </strong>Poly(C) binding protein 2 (PCBP2) was reported to alleviate cardiomyocyte damage, but its molecular mechanism remains unclear. The current study aimed to investigate the role and potential mechanism of PCBP2 in progression of MI.</p><p><strong>Methods: </strong>An in vivo MI model was established by ligation of the left anterior descending (LAD) branch in mice. PCBP2 expression was detected in Normal and MI groups. H9C2 cells were treated with OGD for 0, 2, 4, and 6 h to screen for optimal time to establish MI model in vitro. H9C2 cells were transfected with pcDNA-PCBP2, and the effect of PCBP2 overexpression on OGD-induced oxidative stress, inflammation and ferroptosis was evaluated. Subsequently, the interaction of PCBP2 with NDUFS1 mRNA was predicted by the Starbase database and verified by RNA-immunoprecipitation (RIP) and RNA-protein pull-down assay. Next, a series of reversal experiments were performed to verify the regulation of PCBP2 on NDUFS1 expression. Then, pcDNA-NDUFS1 was transfected into H9C2 and MIND4-17 (NRF2 protein activator) treated for reversal experiments to assess the effect of NDUFS1 on NRF2-mediated ferroptosis. Finally, LV-PCBP2 and LV-NDUFS1 lentiviral vectors were intrapericardially injected into MI mice, and the role of PCBP2 and NDUFS1 in the progression of MI was verified in vivo.</p><p><strong>Results: </strong>PCBP2 was downregulated in MI model and OGD-induced H9C2 cells. PCBP2 improved cell proliferation and inhibited oxidative stress, inflammation and ferroptosis in OGD-incubated H9C2 cells. PCBP2 bound with NDUFS1 mRNA and promoted NDUFS1 expression in H9C2 cells, which promoted NRF2 activation by enhancing NRF2 nuclear translocation and inhibited NRF2-mediated ferroptosis. Finally, administration of LV-PCBP2 and LV-NDUFS1 alleviated myocardial tissue injury and MI infarct in mice through suppressing cardiomyocyte ferroptosis and inflammation.</p><p><strong>Conclusion: </strong>Our results suggested that PCBP2 alleviated MI by inhibiting cardiomyocyte ferroptosis through interacting with NDUFS1 mRNA and activating NRF2-Keap1 pathway.</p>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"186 ","pages":"13-25"},"PeriodicalIF":3.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protocatechuic aldehyde promotes diabetic wound healing by enhancing angiogenesis via H3K18 lactylation-mediated Acvr1c expression","authors":"Weijing Fan ,&nbsp;Yang You ,&nbsp;Yin Qu,&nbsp;Guobin Liu","doi":"10.1016/j.molimm.2025.09.002","DOIUrl":"10.1016/j.molimm.2025.09.002","url":null,"abstract":"<div><div>Delayed wound recovery is a major health issue affecting people with diabetes. Histone lactylation is involved in tissue repair. However, it is not clear whether protocatechuic aldehyde (PCA) promotes diabetic wound healing through histone lactylation. In this study, a diabetic wound mouse model was constructed to delve into the role of PCA in vivo. Chromatin immunoprecipitation sequencing (ChIP-seq) was used to determine genes affected by H3K18 lactylation (H3K18la) under PCA treatment. The effects and mechanisms of PCA on histone lactylation and angiogenesis were investigated through cellular experiments. We found that PCA accelerated wound healing and angiogenesis in diabetic mice, and significantly reduced the inflammatory response in wound tissues. Lactate and H3K18la levels were augmented in the model group in comparison with the control group, however, PCA treatment remarkably reversed their levels. ChIP-seq analysis revealed a significant enrichment of H3K18la at the Acvr1c locus, and this histone modification was downregulated by PCA treatment. PCA remarkably enhanced Acvr1c expression through H3K18la in HUVECs. Moreover, PCA treatment markedly elevated cell viability, migration and tube formation in comparison with the control group. However, this effect was counteracted by Acvr1c knockdown. In conclusion, PCA promoted HUVEC angiogenesis by increasing H3K18la-mediated Acvr1c expression, thereby promoting diabetic wound healing. This could offer a new treatment approach to enhance the effectiveness of healing diabetic wounds.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 152-165"},"PeriodicalIF":3.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145207018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanism of SMAD4/ERK pathway in regulating Th17/Treg cell differentiation leading to olfactory dysfunction in chronic rhinosinusitis","authors":"Shouming Cao ,&nbsp;Yan Niu ,&nbsp;Jinmei Ning ,&nbsp;Nannan Wen ,&nbsp;Rui Chen ,&nbsp;Haiying Wu","doi":"10.1016/j.molimm.2025.09.006","DOIUrl":"10.1016/j.molimm.2025.09.006","url":null,"abstract":"<div><h3>Background</h3><div>Chronic rhinosinusitis (CRS) is characterized by a high recurrence rate within five years post-surgery, posing a persistent challenge for otolaryngologists globally. Recent research has underscored the pivotal role of the Th17/Treg cell balance in the pathogenesis of CRS. This study aims to investigate the alterations in the Th17/Treg cell balance in CRS and elucidate the underlying molecular mechanisms.</div></div><div><h3>Methods</h3><div>CRS model was established to assess the levels of inflammatory cytokines, olfactory marker protein expression, SMAD4 expression, and ERK1/2 phosphorylation. We then overexpressed SMAD4 or treated CRS mice with ERK1/2 inhibitors, measuring the impact on Th17/Treg marker expression. Moreover, the influence of the SMAD4/ERK signaling axis on the Th17/Treg balance within the CD4 + T cell population was investigated.</div></div><div><h3>Results</h3><div>CRS mice exhibited significantly reduced olfactory marker protein and SMAD4 expression, alongside increased ERK1/2 phosphorylation. Histological analysis revealed an increased infiltration of eosinophils. Of particular note, the expression of Treg markers was markedly decreased, while Th17 marker expression exhibited a corresponding increase, suggesting a potential shift in the Th17/Treg balance. Interventions involving SMAD4 overexpression or ERK1/2 inhibition led to a reduction in eosinophil infiltration and successfully reversed the aberrant expression patterns of the aforementioned markers. Furthermore, SMAD4 knockdown resulted in a decreased proportion of Treg cells and an increased proportion of Th17 cells. This alteration in the Th17/Treg balance was effectively counteracted by ERK inhibitor.</div></div><div><h3>Conclusions</h3><div>The deletion of SMAD4 regulates the differentiation of Th17/Treg cells via ERK1/2 phosphorylation, thereby exacerbating the olfactory dysfunction of CRS.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 142-151"},"PeriodicalIF":3.0,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145154974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic targeting of neuroinflammation in sphingolipidosis","authors":"Ebru Ada ,&nbsp;Volkan Seyrantepe","doi":"10.1016/j.molimm.2025.09.005","DOIUrl":"10.1016/j.molimm.2025.09.005","url":null,"abstract":"<div><div>Lysosomal storage diseases (LSDs) are a class of hereditary metabolic disorders primarily caused by lysosomal enzyme defects, leading to the accumulation of undegraded substrates. Sphingolipidoses, a subset of LSDs, are primarily associated with profound involvement of the central nervous system (CNS), characterized by progressive neurodegeneration due to massive sphingolipid accumulation. A common pathological feature among many CNS-involved LSDs is the early activation of microglia and astrocytes, which often precedes and predicts regions of subsequent neuronal loss. The extent to which neuroinflammation disrupts CNS homeostasis appears to be determined by its onset, magnitude, and duration. Although neuroinflammatory processes are increasingly recognized as critical contributors to disease progression in sphingolipidoses, the molecular mechanisms underlying glial activation and the initiation of inflammatory cascades remain incompletely understood. Therefore, mouse models of sphingolipidoses have been instrumental in elucidating these pathogenic processes and provide valuable platforms for evaluating therapeutic strategies. This review critically examines the role of neuroinflammation in sphingolipidoses, summarizes insights derived from pre-clinical models, and discusses the therapeutic potential of anti-inflammatory interventions to mitigate CNS pathology and improve clinical outcomes.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 121-133"},"PeriodicalIF":3.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypocontractile airway smooth muscle phenotype exhibits enhanced β2 laminin chain expression in lung allergy model","authors":"Ivonne Pacheco-Alba ,&nbsp;Blanca Bazán-Perkins","doi":"10.1016/j.molimm.2025.09.003","DOIUrl":"10.1016/j.molimm.2025.09.003","url":null,"abstract":"<div><div>Sensitization with ovalbumin (OVA) in guinea pigs to induce anti-OVA IgE generates various allergic response phenotypes. One phenotype, characterized by the absence of bronchial obstruction and airway hyperresponsiveness in response to chronic antigen challenge, is termed non-responding (NR) and exhibits high IFN-γ levels. The Th1 cytokine profile is linked with high laminin β2 expression. This study evaluated laminin β2 expression in the chronic NR phenotype. Guinea pigs were sensitized and challenged with OVA three times (acute) or twelve times (chronic). Guinea pigs that responded to all challenges formed the asthma model phenotype. Controls were sensitized and challenged with saline. Immunohistochemistry was used to observe laminin β2 and its receptor, the α6 integrin subunit, in bronchial and arterial intrapulmonary smooth muscles. Only chronic NR guinea pigs showed increased laminin β2 expression in these muscles, while it remained similar in other groups. The α6 integrin subunit significantly increased in the acute and chronic asthma models, chronic controls, and NR guinea pigs in bronchial smooth muscle. In arterial intrapulmonary smooth muscle, the α6 integrin subunit increased in acute NR and chronic asthma model guinea pigs. The expression of laminin β2 in bronchial and arterial intrapulmonary smooth muscles correlates with α6 integrin subunit levels, and higher levels of laminin β2 were significantly related to reduced antigen-induced bronchial obstruction and reactivity to histamine. The expression of these proteins does not affect the proliferation of pulmonary blood vessels. Laminin β2 chain overexpression is likely involved in the chronic containment of the obstructive allergic response.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 134-141"},"PeriodicalIF":3.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monochromatic green light-mediated melatonin promotes cecal barrier function in broilers","authors":"Tao Quan,&nbsp;Ran Li,&nbsp;Yaoxing Chen,&nbsp;Ting Gao","doi":"10.1016/j.molimm.2025.09.004","DOIUrl":"10.1016/j.molimm.2025.09.004","url":null,"abstract":"<div><div>Light plays a crucial role as an environmental factor, greatly affecting chick behavior, production performance and health. Melatonin, an essential marker of photoelectric signaling, plays a role in regulating various physiological functions in broilers, such as gut health. However, whether monochromatic light can mediate melatonin secretion to regulate intestinal function and its regulatory mechanism are not known. In the present study, we showed that monochromatic green light significantly enhanced the mucosal barrier function of the broiler cecum, including the up-regulation of goblet cells and their secreted MUC2 content, tight junction protein expression and enterocyte proliferative viability. However, when the pineal gland was removed, accompanied by a decrease in melatonin content, the green light advantage disappeared and the intestinal mucosal barrier function was severely impaired. Mechanistically, we found that monochromatic green light promotes melatonin secretion, which enters the intestine to bind Mel1a receptors located on macrophage membranes in cecum, inhibits its downstream TLR4/ERK/JNK/NF-κB signaling pathway, promotes M2-type macrophage polarization, reduces intestinal inflammation levels while up-regulating intestinal antioxidant levels, and ultimately strengthens the cecum mucosal barrier function. Our findings provide new theoretical support for the future use of melatonin during intestinal development, as well as theoretical guidance for the proper application of artificial lighting in the modern chicken industry to improve chicken's intestinal health.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 109-120"},"PeriodicalIF":3.0,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145099353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the heterogeneity in oxidative stress and transcriptional programs within the in vivo microenvironment of ulcerative colitis","authors":"Yongwei Zhuang ,&nbsp;Ran Ye ,&nbsp;Jingyu Chen ,&nbsp;Gefei Chen ,&nbsp;Luyi Chen ,&nbsp;Yabi Zhu ,&nbsp;Shufang Ye ,&nbsp;Yangyang Liu","doi":"10.1016/j.molimm.2025.08.017","DOIUrl":"10.1016/j.molimm.2025.08.017","url":null,"abstract":"<div><h3>Objective</h3><div>Oxidative stress exerts an essential role in the pathogenesis of ulcerative colitis (UC). This study aims to unveil the heterogeneity in oxidative stress among immune cell subpopulations in UC.</div></div><div><h3>Methods</h3><div>Human colon epithelial cells were exposed to 100 ng/mL LPS to stimulate UC, which were administrated with antioxidants 500 mM butylated hydroxyanisole or 20 μM N-acetylcysteine. A single-cell atlas was constructed across UC, and heterogeneous cell subpopulations were evaluated at single-cell and bulk levels.</div></div><div><h3>Results</h3><div>Activation of oxidative stress and inflammatory response, enhanced migration capacity, and impaired tight junction were observed in LPS-induced UC cell models, which were ameliorated by antioxidants. Five cell types: plasma cells, T cells, myeloid cells, and B cells were clustered across UC and control gut biopsies, which were tightly interacted. Myeloid cells were sub-clustered into conventional dendritic cells, M1 macrophages, IL23R⁺ myeloid cells, mast cells, and follicular dendritic cells; T cells were sub-clustered into Th17, CD4⁺ naïve T cells, CD8⁺ cytotoxic T cells, CD4⁺ exhausted T cells, CD8⁺ memory T cells, Tregs, and Th1. The heterogeneous myeloid and T cells was confirmed at the single-cell and bulk levels. The activity of oxidative stress was heterogeneous among diverse myeloid cell or T cell subpopulations, with the strongest activity in M1 macrophages and CD4⁺ exhausted T cells, respectively. It was also found the specific transcriptional programs of M1 macrophages and CD8⁺ cytotoxic T cells.</div></div><div><h3>Conclusion</h3><div>Overall, our findings unveil the heterogeneity in oxidative stress and transcriptional programs among diverse myeloid and T cell subpopulations in UC.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 80-95"},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiling of SFTS virus and host protein interactions by affinity purification-mass spectrometry","authors":"Wen Hou ,&nbsp;Jiansen Lu ,&nbsp;Hao Pan ,&nbsp;Tao Wang ,&nbsp;Hongyun Liu ,&nbsp;Ruibing Chen","doi":"10.1016/j.molimm.2025.09.001","DOIUrl":"10.1016/j.molimm.2025.09.001","url":null,"abstract":"<div><div>Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the novel phlebovirus SFTSV (SFTS bunyavirus), was first identified in 2009 across several Chinese provinces, with a case fatality rate reaching 30 %. Given its compact genome, SFTSV critically depends on host cellular machinery for replication and pathogenesis. In this study, we employed a systematic strategy combining co-immunoprecipitation of viral-host complexes with formaldehyde crosslinking and affinity purification-mass spectrometry (AP-MS) to comprehensively map SFTSV-host interactions. We systematically analyzed protein complexes associated with all five viral structural/non-structural proteins (NP, NSs, Gc, Gn, and L), identifying 432 host proteins as potential viral interactors. Subsequent bioinformatic analysis included Gene Ontology categorization and functional domain/pathway enrichment analysis via KEGG, with interaction networks visualized through Cytoscape. Importantly, we experimentally validated key interactions between NSs and host proteins VDAC1, Vimentin, and HSP90AB1, demonstrating robust consistency with our mass spectrometry findings.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"187 ","pages":"Pages 96-108"},"PeriodicalIF":3.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}