Journal of immunology最新文献_第10页

Potent HPIV3-neutralizing IGHV5-51 Antibodies Identified from Multiple Individuals Show L Chain and CDRH3 Promiscuity. 从多个个体中鉴定出的强效 HPIV3 中和 IGHV5-51 抗体显示出 L 链和 CDRH3 的杂合性。

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-05-01 DOI: 10.4049/jimmunol.2300880

Alexandra A Abu-Shmais, Rose J Miller, Alexis K Janke, Rachael M Wolters, Clinton M Holt, Nagarajan Raju, Robert H Carnahan, James E Crowe, Jarrod J Mousa, Ivelin S Georgiev

{"title":"Potent HPIV3-neutralizing IGHV5-51 Antibodies Identified from Multiple Individuals Show L Chain and CDRH3 Promiscuity.","authors":"Alexandra A Abu-Shmais, Rose J Miller, Alexis K Janke, Rachael M Wolters, Clinton M Holt, Nagarajan Raju, Robert H Carnahan, James E Crowe, Jarrod J Mousa, Ivelin S Georgiev","doi":"10.4049/jimmunol.2300880","DOIUrl":"10.4049/jimmunol.2300880","url":null,"abstract":"Human parainfluenza virus 3 (HPIV3) is a widespread pathogen causing severe and lethal respiratory illness in at-risk populations. Effective countermeasures are in various stages of development; however, licensed therapeutic and prophylactic options are not available. The fusion glycoprotein (HPIV3 F), responsible for facilitating viral entry into host cells, is a major target of neutralizing Abs that inhibit infection. Although several neutralizing Abs against a small number of HPIV3 F epitopes have been identified to date, relatively little is known about the Ab response to HPIV3 compared with other pathogens, such as influenza virus and SARS-CoV-2. In this study, we aimed to characterize a set of HPIV3-specific Abs identified in multiple individuals for genetic signatures, epitope specificity, neutralization potential, and publicness. We identified 12 potently neutralizing Abs targeting three nonoverlapping epitopes on HPIV3 F. Among these, six Abs identified from two different individuals used Ig heavy variable gene IGHV 5-51, with five of the six Abs targeting the same epitope. However, despite the use of the same H chain variable (VH) gene, these Abs used multiple different L chain variable genes (VL) and diverse H chain CDR 3 (CDRH3) sequences. Together, these results provide further information about the genetic and functional characteristics of HPIV3-neutralizing Abs and suggest the existence of a reproducible VH-dependent Ab response associated with VL and CDRH3 promiscuity. Understanding sites of HPIV3 F vulnerability and the genetic and molecular characteristics of Abs targeting these sites will help guide efforts for effective vaccine and therapeutic development.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1450-1456"},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sensitization with Fungal Protease Allergen Establishes Long-Lived, Allergenic Th Cell Memory in the Lung. 真菌蛋白酶过敏原致敏可在肺部建立长效过敏性Th细胞记忆

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-05-01 DOI: 10.4049/jimmunol.2300694

Abigail Shapiro, Nicolas W S Caballes, Rebecca N Vera, Bruce S Klein, Paul J Brennan, Yen-Fei Wu, Darin L Wiesner

{"title":"Sensitization with Fungal Protease Allergen Establishes Long-Lived, Allergenic Th Cell Memory in the Lung.","authors":"Abigail Shapiro, Nicolas W S Caballes, Rebecca N Vera, Bruce S Klein, Paul J Brennan, Yen-Fei Wu, Darin L Wiesner","doi":"10.4049/jimmunol.2300694","DOIUrl":"10.4049/jimmunol.2300694","url":null,"abstract":"Allergic asthma is a chronic inflammatory disease that affects millions of individuals worldwide. Exposure to allergens produced by a variety of otherwise harmless microbes, including fungi, predisposes individuals to immunopathologic disease upon subsequent encounters with allergen. We developed a mouse model that employs a purified protease produced by Aspergillus (Asp f 13) to investigate the contributions of CD4+ Th cells to recurrent lung inflammation. Notably, memory CD4+ T cells enhanced the eosinophil response of sensitized/rechallenged animals. In addition, memory CD4+ T cells maintained allergenic features, including expression of GATA-binding protein 3 and IL-5. Th2 memory T cells persisted in the peribronchiolar interstitium of the lung and expressed markers of tissue residence, such as CD69, CCR8, and IL-33R. Lastly, we identified a peptide epitope contained within Asp f 13 and generated a peptide-MHC class II tetramer. Using these tools, we further demonstrated the durability and exquisite sensitivity of memory T cells in promoting lung eosinophilia. Our data highlight important features of memory T cells that strengthen the notion that memory T cells are principal drivers of eosinophilic disease in murine models of allergic sensitization and episodic airway inflammation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1420-1427"},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11037450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antibody-Suppressor CXCR5+CD8+ T Cells Are More Potent Regulators of Humoral Alloimmunity after Kidney Transplant in Mice Compared to CD4+ Regulatory T Cells. 与 CD4+ 调节性 T 细胞相比，抗体抑制性 CXCR5+CD8+ T 细胞是小鼠肾移植后体液异体免疫的更有效调节因子。

IF 4.4 3区医学

Journal of immunology Pub Date : 2024-05-01 DOI: 10.4049/jimmunol.2300289

Jing L Han, Jason M Zimmerer, Qiang Zeng, Sachi Chaudhari, Anjali Satoskar, Mahmoud Abdel-Rasoul, Hope Uwase, Christopher K Breuer, Ginny L Bumgardner

{"title":"Antibody-Suppressor CXCR5+CD8+ T Cells Are More Potent Regulators of Humoral Alloimmunity after Kidney Transplant in Mice Compared to CD4+ Regulatory T Cells.","authors":"Jing L Han, Jason M Zimmerer, Qiang Zeng, Sachi Chaudhari, Anjali Satoskar, Mahmoud Abdel-Rasoul, Hope Uwase, Christopher K Breuer, Ginny L Bumgardner","doi":"10.4049/jimmunol.2300289","DOIUrl":"10.4049/jimmunol.2300289","url":null,"abstract":"Adoptive cell therapy (ACT), especially with CD4+ regulatory T cells (CD4+ Tregs), is an emerging therapeutic strategy to minimize immunosuppression and promote long-term allograft acceptance, although much research remains to realize its potential. In this study, we investigated the potency of novel Ab-suppressor CXCR5+CD8+ T cells (CD8+ TAb-supp) in comparison with conventional CD25highFoxp3+CD4+ Tregs for suppression of humoral alloimmunity in a murine kidney transplant (KTx) model of Ab-mediated rejection (AMR). We examined quantity of peripheral blood, splenic and graft-infiltrating CD8+ TAb-supp, and CD4+ Tregs in KTx recipients and found that high alloantibody-producing CCR5 knockout KTx recipients have significantly fewer post-transplant peripheral blood and splenic CD8+ TAb-supp, as well as fewer splenic and graft-infiltrating CD4+ Tregs compared with wild-type KTx recipients. ACT with alloprimed CXCR5+CD8+ T cells reduced alloantibody titer, splenic alloprimed germinal center (GC) B cell quantity, and improved AMR histology in CCR5 knockout KTx recipients. ACT with alloprimed CD4+ Treg cells improved AMR histology without significantly inhibiting alloantibody production or the quantity of splenic alloprimed GC B cells. Studies with TCR transgenic mice confirmed Ag specificity of CD8+ TAb-supp-mediated effector function. In wild-type recipients, CD8 depletion significantly increased alloantibody titer, GC B cells, and severity of AMR pathology compared with isotype-treated controls. Anti-CD25 mAb treatment also resulted in increased but less pronounced effect on alloantibody titer, quantity of GC B cells, and AMR pathology than CD8 depletion. To our knowledge, this is the first report that CD8+ TAb-supp cells are more potent regulators of humoral alloimmunity than CD4+ Treg cells.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1504-1518"},"PeriodicalIF":4.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11047759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140184622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential. CD4 T细胞衍生的IL-21对维持疟原虫感染诱导的生殖中心反应和促进具有回忆潜能的记忆B细胞的选择至关重要。

IF 4.4 3区医学

Journal of immunology Pub Date : 2024-05-01 DOI: 10.4049/jimmunol.2300683

Jordan T Johnson, Fionna A Surette, Graham R Ausdal, Manan Shah, Allen M Minns, Scott E Lindner, Ryan A Zander, Noah S Butler

{"title":"CD4 T Cell-Derived IL-21 Is Critical for Sustaining Plasmodium Infection-Induced Germinal Center Responses and Promoting the Selection of Memory B Cells with Recall Potential.","authors":"Jordan T Johnson, Fionna A Surette, Graham R Ausdal, Manan Shah, Allen M Minns, Scott E Lindner, Ryan A Zander, Noah S Butler","doi":"10.4049/jimmunol.2300683","DOIUrl":"10.4049/jimmunol.2300683","url":null,"abstract":"Development of Plasmodium-specific humoral immunity is critically dependent on CD4 Th cell responses and germinal center (GC) reactions during blood-stage Plasmodium infection. IL-21, a cytokine primarily produced by CD4 T cells, is an essential regulator of affinity maturation, isotype class-switching, B cell differentiation, and maintenance of GC reactions in response to many infection and immunization models. In models of experimental malaria, mice deficient in IL-21 or its receptor IL-21R fail to develop memory B cell populations and are not protected against secondary infection. However, whether sustained IL-21 signaling in ongoing GCs is required for maintaining GC magnitude, organization, and output is unclear. In this study, we report that CD4+ Th cells maintain IL-21 expression after resolution of primary Plasmodium yoelii infection. We generated an inducible knockout mouse model that enabled cell type-specific and timed deletion of IL-21 in peripheral, mature CD4 T cells. We found that persistence of IL-21 signaling in active GCs had no impact on the magnitude of GC reactions or their capacity to produce memory B cell populations. However, the memory B cells generated in the absence of IL-21 exhibited reduced recall function upon challenge. Our data support that IL-21 prevents premature cellular dissolution within the GC and promotes stringency of selective pressures during B cell fate determination required to produce high-quality Plasmodium-specific memory B cells. These data are additionally consistent with a temporal requirement for IL-21 in fine-tuning humoral immune memory responses during experimental malaria.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1467-1478"},"PeriodicalIF":4.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Top Reads. 热门阅读

IF 4.4 3区医学

Journal of immunology Pub Date : 2024-05-01 DOI: 10.4049/jimmunol.2490002

引用次数: 0

PRMT5 Promotes T follicular helper Cell Differentiation and Germinal Center Responses during Influenza Virus Infection. PRMT5 在流感病毒感染过程中促进 T 滤泡辅助细胞分化和生殖中心反应

IF 3.6 3区医学

Journal of immunology Pub Date : 2024-05-01 DOI: 10.4049/jimmunol.2300270

Kaitlin A Read, Stephanie A Amici, Sadaf Farsi, Madeline Cutcliffe, Bella Lee, Chan-Wang Jerry Lio, Hsin-Jung Joyce Wu, Mireia Guerau-de-Arellano, Kenneth J Oestreich

{"title":"PRMT5 Promotes T follicular helper Cell Differentiation and Germinal Center Responses during Influenza Virus Infection.","authors":"Kaitlin A Read, Stephanie A Amici, Sadaf Farsi, Madeline Cutcliffe, Bella Lee, Chan-Wang Jerry Lio, Hsin-Jung Joyce Wu, Mireia Guerau-de-Arellano, Kenneth J Oestreich","doi":"10.4049/jimmunol.2300270","DOIUrl":"10.4049/jimmunol.2300270","url":null,"abstract":"Protein arginine methyltransferases (PRMTs) modify diverse protein targets and regulate numerous cellular processes; yet, their contributions to individual effector T cell responses during infections are incompletely understood. In this study, we identify PRMT5 as a critical regulator of CD4+ T follicular helper cell (Tfh) responses during influenza virus infection in mice. Conditional PRMT5 deletion in murine T cells results in an almost complete ablation of both Tfh and T follicular regulatory populations and, consequently, reduced B cell activation and influenza-specific Ab production. Supporting a potential mechanism, we observe elevated surface expression of IL-2Rα on non-T regulatory effector PRMT5-deficient T cells. Notably, IL-2 signaling is known to negatively impact Tfh differentiation. Collectively, our findings identify PRMT5 as a prominent regulator of Tfh programming, with potential causal links to IL-2 signaling.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1442-1449"},"PeriodicalIF":3.6,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High-Affinity-Mediated Viral Entry Triggers Innate Affinity Escape Resulting in Type I IFN Resistance and Impaired T Cell Immunity. 高亲和力病毒进入引发先天亲和力逃逸，导致 I 型 IFN 抗性和 T 细胞免疫受损。

IF 4.4 3区医学

Journal of immunology Pub Date : 2024-05-01 DOI: 10.4049/jimmunol.2300637

Haifeng C Xu, Piyush Pandey, Harry Ward, Michal Gorzkiewicz, Džiuljeta Abromavičiūtė, Constanze Tinz, Lisa Müller, Caroline Meyer, Aleksandra A Pandyra, Aslihan Yavas, Arndt Borkhardt, Irene Esposito, Karl S Lang, Philipp A Lang

{"title":"High-Affinity-Mediated Viral Entry Triggers Innate Affinity Escape Resulting in Type I IFN Resistance and Impaired T Cell Immunity.","authors":"Haifeng C Xu, Piyush Pandey, Harry Ward, Michal Gorzkiewicz, Džiuljeta Abromavičiūtė, Constanze Tinz, Lisa Müller, Caroline Meyer, Aleksandra A Pandyra, Aslihan Yavas, Arndt Borkhardt, Irene Esposito, Karl S Lang, Philipp A Lang","doi":"10.4049/jimmunol.2300637","DOIUrl":"10.4049/jimmunol.2300637","url":null,"abstract":"Increased receptor binding affinity may allow viruses to escape from Ab-mediated inhibition. However, how high-affinity receptor binding affects innate immune escape and T cell function is poorly understood. In this study, we used the lymphocytic choriomeningitis virus (LCMV) murine infection model system to create a mutated LCMV exhibiting higher affinity for the entry receptor α-dystroglycan (LCMV-GPH155Y). We show that high-affinity receptor binding results in increased viral entry, which is associated with type I IFN (IFN-I) resistance, whereas initial innate immune activation was not impaired during high-affinity virus infection in mice. Consequently, IFN-I resistance led to defective antiviral T cell immunity, reduced type II IFN, and prolonged viral replication in this murine model system. Taken together, we show that high-affinity receptor binding of viruses can trigger innate affinity escape including resistance to IFN-I resulting in prolonged viral replication.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1457-1466"},"PeriodicalIF":4.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11016594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transient Binding Dynamics of Complement System Pattern Recognition Molecules on Pathogens. 病原体上补体系统模式识别分子的瞬时结合动力学。

IF 4.4 3区医学

Journal of immunology Pub Date : 2024-05-01 DOI: 10.4049/jimmunol.2300768

Maximilian Peter Götz, Mario Alejandro Duque Villegas, Beatrice Fageräng, Aileen Kerfin, Mikkel-Ole Skjoedt, Peter Garred, Anne Rosbjerg

{"title":"Transient Binding Dynamics of Complement System Pattern Recognition Molecules on Pathogens.","authors":"Maximilian Peter Götz, Mario Alejandro Duque Villegas, Beatrice Fageräng, Aileen Kerfin, Mikkel-Ole Skjoedt, Peter Garred, Anne Rosbjerg","doi":"10.4049/jimmunol.2300768","DOIUrl":"10.4049/jimmunol.2300768","url":null,"abstract":"Previous studies of pattern recognition molecules (PRMs) of the complement system have revealed difficulties in observing binding on pathogens such as Aspergillus fumigatus and Escherichia coli, despite complement deposition indicative of classical and lectin pathway activation. Thus, we investigated the binding dynamics of PRMs of the complement system, specifically C1q of the classical pathway and mannose-binding lectin (MBL) of the lectin pathway. We observed consistently increasing deposition of essential complement components such as C4b, C3b, and the terminal complement complex on A. fumigatus and E. coli. However, C1q and MBL binding to the surface rapidly declined during incubation after just 2-4 min in 10% plasma. The detachment of C1q and MBL can be linked to complement cascade activation, as the PRMs remain bound in the absence of plasma. The dissociation and the fate of C1q and MBL seem to have different mechanistic functions. Notably, C1q dynamics were associated with local C1 complex activation. When C1s was inhibited in plasma, C1q binding not only remained high but further increased over time. In contrast, MBL binding was inversely correlated with total and early complement activation due to MBL binding being partially retained by complement inhibition. Results indicate that detached MBL might be able to functionally rebind to A. fumigatus. In conclusion, these results reveal a (to our knowledge) novel \"hit-and-run\" complement-dependent PRM dynamic mechanism on pathogens. These dynamics may have profound implications for host defense and may help increase the functionality and longevity of complement-dependent PRMs in circulation.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1493-1503"},"PeriodicalIF":4.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131724","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}

引用次数: 0

Regulation of Tumor Dendritic Cells by Programmed Cell Death 1 Pathways. 程序性细胞死亡 1 通路对肿瘤树突状细胞的调控

IF 4.4 3区医学

Journal of immunology Pub Date : 2024-05-01 DOI: 10.4049/jimmunol.2300674

Keith L Knutson

{"title":"Regulation of Tumor Dendritic Cells by Programmed Cell Death 1 Pathways.","authors":"Keith L Knutson","doi":"10.4049/jimmunol.2300674","DOIUrl":"https://doi.org/10.4049/jimmunol.2300674","url":null,"abstract":"The advent of immune checkpoint blockade therapy has revolutionized cancer treatments and is partly responsible for the significant decline in cancer-related mortality observed during the last decade. Immune checkpoint inhibitors, such as anti-programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1), have demonstrated remarkable clinical successes in a subset of cancer patients. However, a considerable proportion of patients remain refractory to immune checkpoint blockade, prompting the exploration of mechanisms of treatment resistance. Whereas much emphasis has been placed on the role of PD-L1 and PD-1 in regulating the activity of tumor-infiltrating T cells, recent studies have now shown that this immunoregulatory axis also directly regulates myeloid cell activity in the tumor microenvironment including tumor-infiltrating dendritic cells. In this review, I discuss the most recent advances in the understanding of how PD-1, PD-L1, and programmed cell death ligand 2 regulate the function of tumor-infiltrating dendritic cells, emphasizing the need for further mechanistic studies that could facilitate the development of novel combination immunotherapies for improved cancer patient benefit.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":"212 9","pages":"1397-1405"},"PeriodicalIF":4.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140864002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chicken UFL1 Restricts Avian Influenza Virus Replication by Disrupting the Viral Polymerase Complex and Facilitating Type I IFN Production. 鸡 UFL1 通过破坏病毒聚合酶复合体和促进 I 型 IFN 的产生来限制禽流感病毒的复制。

IF 4.4 3区医学

Journal of immunology Pub Date : 2024-05-01 DOI: 10.4049/jimmunol.2300613

Weiqiang Li, Yu Lin, Xiyi Wang, Huixing Yang, Yangbao Ding, Zuxian Chen, Zhuoliang He, Junsheng Zhang, Luxiang Zhao, Peirong Jiao

{"title":"Chicken UFL1 Restricts Avian Influenza Virus Replication by Disrupting the Viral Polymerase Complex and Facilitating Type I IFN Production.","authors":"Weiqiang Li, Yu Lin, Xiyi Wang, Huixing Yang, Yangbao Ding, Zuxian Chen, Zhuoliang He, Junsheng Zhang, Luxiang Zhao, Peirong Jiao","doi":"10.4049/jimmunol.2300613","DOIUrl":"10.4049/jimmunol.2300613","url":null,"abstract":"During avian influenza virus (AIV) infection, host defensive proteins promote antiviral innate immunity or antagonize viral components to limit viral replication. UFM1-specific ligase 1 (UFL1) is involved in regulating innate immunity and DNA virus replication in mammals, but the molecular mechanism by which chicken (ch)UFL1 regulates AIV replication is unclear. In this study, we first identified chUFL1 as a negative regulator of AIV replication by enhancing innate immunity and disrupting the assembly of the viral polymerase complex. Mechanistically, chUFL1 interacted with chicken stimulator of IFN genes (chSTING) and contributed to chSTING dimerization and the formation of the STING-TBK1-IRF7 complex. We further demonstrated that chUFL1 promoted K63-linked polyubiquitination of chSTING at K308 to facilitate chSTING-mediated type I IFN production independent of UFMylation. Additionally, chUFL1 expression was upregulated in response to AIV infection. Importantly, chUFL1 also interacted with the AIV PA protein to inhibit viral polymerase activity. Furthermore, chUFL1 impeded the nuclear import of the AIV PA protein and the assembly of the viral polymerase complex to suppress AIV replication. Collectively, these findings demonstrate that chUFL1 restricts AIV replication by disrupting the viral polymerase complex and facilitating type I IFN production, which provides new insights into the regulation of AIV replication in chickens.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":"1479-1492"},"PeriodicalIF":4.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140110419","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}

引用次数: 0