ACS Infectious Diseases最新文献_第10页

Honoring a Legacy: "Vigyan Ratna" Prof. G. Padmanaban. 向遗产致敬："Vigyan Ratna"（维吉安-拉特纳）G. Padmanaban 教授。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-08 Epub Date: 2024-10-03 DOI: 10.1021/acsinfecdis.4c00759

Varadharajan Sundaramurthy, Jayanta Haldar

引用次数: 0

Overexpression of l,d-Transpeptidase A Induces Dispensability of Rod Complex in Escherichia coli. 过量表达 l,d-转肽酶 A 可诱导大肠杆菌中的杆状复合体失去功能。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-08 Epub Date: 2024-10-16 DOI: 10.1021/acsinfecdis.4c00597

Rinki Gupta, Timsy Bhando, Ranjana Pathania

{"title":"Overexpression of l,d-Transpeptidase A Induces Dispensability of Rod Complex in Escherichia coli.","authors":"Rinki Gupta, Timsy Bhando, Ranjana Pathania","doi":"10.1021/acsinfecdis.4c00597","DOIUrl":"10.1021/acsinfecdis.4c00597","url":null,"abstract":"Antimicrobial resistance (AMR) is a significant global threat, and the presence of resistance-determinant genes is one of the major driving forces behind it. The bacterial rod complex is an essential set of proteins that is crucial for cell survival due to its role in cell wall biogenesis and shape maintenance. Therefore, these proteins offer excellent potential as drug targets; however, compensatory mutations in nontarget genes render this complex nonessential. The MreB protein of this complex is an actin homologue that rotates along the longitudinal axis of the cell to provide rod shape to the bacteria. In this study, using chemical-chemical interaction profiling and FtsZ suppression assay, we identified the MreB targeting activity of IITR07865, a previously discovered small molecule in our lab. Escherichia coli suppressors against IITR07865 revealed mutations in two cell division-associated genes, min C and pal, that have not been previously implicated in rod complex essentiality. IITR07865 resistant mutants were found to inactivate and render the rod complex nonessential, making the rod complex inhibitors ineffective. Further, through transcriptome analysis, we reveal the primary cause of resistance in suppressor strains to be the overexpression of an l, d-transpeptidase A enzyme, which is involved in peptidoglycan and Braun's lipoprotein cross-linking. Our results demonstrate a novel mechanism of resistance development in rod-shaped Gram-negative bacterial pathogen E. coli involved in UTIs where mecillinam, a clinically used antibiotic that targets rod complex, is a drug of choice.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3928-3938"},"PeriodicalIF":4.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Self-Adjuvanting Adenoviral Nanovaccine for Effective T-Cell-Mediated Immunity and Long-Lasting Memory Cell Activation against Tuberculosis. 自佐剂腺病毒纳米疫苗可有效增强T细胞介导的免疫力并激活持久的结核病记忆细胞。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-08 Epub Date: 2024-10-28 DOI: 10.1021/acsinfecdis.4c00619

Chithaiyan Kamaladevi Sowndharya, Sivaraj Mehnath, Arivalagan Ponbharathi, Murugaraj Jeyaraj

{"title":"Self-Adjuvanting Adenoviral Nanovaccine for Effective T-Cell-Mediated Immunity and Long-Lasting Memory Cell Activation against Tuberculosis.","authors":"Chithaiyan Kamaladevi Sowndharya, Sivaraj Mehnath, Arivalagan Ponbharathi, Murugaraj Jeyaraj","doi":"10.1021/acsinfecdis.4c00619","DOIUrl":"10.1021/acsinfecdis.4c00619","url":null,"abstract":"An enhanced vaccine is immediately required to swap the more than 100 year-old bacillus Calmette-Guerin (BCG) vaccine against tuberculosis. Here, trimethyl chitosan-loaded inactivated Mycobacterium smegmatis (MST), along with potent adenovirus hexon protein (AdHP), and toll-like receptor (TLR)-1/2 as a nanovaccine, was developed against tuberculosis (TB). The nanoformulation increased the bioavailability of MST and elicited the targeting ability. Nanovaccines have a size range of 183.5 ± 9.5 nm with a spherical morphology and uniform distribution. The nanovaccine exhibited a higher release of antigen in acidic pH, and this is mainly due to protonation of ionizable groups in polymeric materials. The nanovaccine facilitated the effective cellular uptake of bone-marrow-derived dendritic cells and progressive endosomal escape in a shorter period. In vitro analyses indicated that the nanovaccine activated cytokine and T-cell production and also assisted in humoral immunity by producing antibodies. The nanovaccine was able to induce more cellular and humoral memory cells and a better protective immune response. Nanomaterials effectively delivered the MST, AdHP, and TLR1/2 antigens to the major histocompatibility complex class I and II pathways to generate protective cytotoxic CD8+ and CD4+ T-cells. In vivo experiments, compared with free MST and BCG, showed that mice immunized with the nanovaccine induced more specific CD4+, CD8+, and memory T-cell activations. Overall, the fabricated nanovaccine was able to control the release of antigens and adjuvants and enhance memory cell activation and humoral immunity against TB.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3939-3950"},"PeriodicalIF":4.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Modulators of the Hop-HSP90 Protein-Protein Interaction Disrupt KSHV Lytic Replication. Hop-HSP90蛋白-蛋白相互作用的调节剂会破坏KSHV的溶解复制

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-08 Epub Date: 2024-10-30 DOI: 10.1021/acsinfecdis.4c00429

Michael O Okpara, Michaelone C Vaaltyn, Jessica L Watson, Mahama Alhassan, Fernando Albericio, Beatriz G de la Torre, David J Clarke, Clinton G L Veale, Adrienne L Edkins

{"title":"Modulators of the Hop-HSP90 Protein-Protein Interaction Disrupt KSHV Lytic Replication.","authors":"Michael O Okpara, Michaelone C Vaaltyn, Jessica L Watson, Mahama Alhassan, Fernando Albericio, Beatriz G de la Torre, David J Clarke, Clinton G L Veale, Adrienne L Edkins","doi":"10.1021/acsinfecdis.4c00429","DOIUrl":"10.1021/acsinfecdis.4c00429","url":null,"abstract":"The central role of the chaperome in maintaining cellular proteostasis has seen numerous viral families evolve to parasitically exploit host chaperones in their life cycle. The HSP90 chaperone protein and its cochaperone Hop have both individually been shown to be essential factors for Kaposi sarcoma-associated herpesvirus (KSHV) lytic replication. Given the fundamental regulatory role that protein-protein interactions (PPIs) play in cellular biology, we reasoned that disrupting the Hop-HSP90 PPI may provide a new host-based target for inhibiting KSHV lytic replication. This study expands upon a previous report of non-natural peptides, which were found to disrupt the association between the HopTPR2A domain and its interacting HSP90CTD. Here, in addition to providing insight into the structure-activity relationships of PPI inhibition, we show disruption of the full-length Hop-HSP90 PPI. The inhibitory peptides selectively engaged the HopTPR2A domain in cell lysates and when tethered to a cell-penetrating peptide acted as noncytotoxic inhibitors of KSHV lytic replication by lowering the viral load, preventing the production of infectious virions, and reducing the expression of KSHV lytic genes. In addition to tentative evidence of Hop-HSP90 PPI as a much-needed target for KSHV drug discovery, this study represents an important step in understanding viral interactions with the host proteostasis machinery.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3853-3867"},"PeriodicalIF":4.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Call for Papers: The Role of Microbiota in Infection and Immunity. 征集论文：微生物群在感染和免疫中的作用。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-08 Epub Date: 2024-10-30 DOI: 10.1021/acsinfecdis.4c00841

Matthew Griffin, Stavroula Hatzios, Yuan Qiao

引用次数: 0

Quaternized 1,2,3-Triazolyl Content and Modulation Potentiate Antibacterial and Antifungal Activities of Amphipathic Peptoids. 季铵化 1,2,3-三唑含量和调制可增强两性肽的抗菌和抗真菌活性。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-08 Epub Date: 2024-10-11 DOI: 10.1021/acsinfecdis.4c00591

Cassandra Guerinot, Mélodie Malige, Kathakali De, Marc Maresca, Nicolas Charbonnel, Elise Courvoisier-Dezord, Nicolas Vidal, Olivier Roy, Frederic Laurent, Jérôme Josse, Christopher Aisenbrey, Burkhard Bechinger, Christiane Forestier, Sophie Faure

{"title":"Quaternized 1,2,3-Triazolyl Content and Modulation Potentiate Antibacterial and Antifungal Activities of Amphipathic Peptoids.","authors":"Cassandra Guerinot, Mélodie Malige, Kathakali De, Marc Maresca, Nicolas Charbonnel, Elise Courvoisier-Dezord, Nicolas Vidal, Olivier Roy, Frederic Laurent, Jérôme Josse, Christopher Aisenbrey, Burkhard Bechinger, Christiane Forestier, Sophie Faure","doi":"10.1021/acsinfecdis.4c00591","DOIUrl":"10.1021/acsinfecdis.4c00591","url":null,"abstract":"Bioinspired from cationic antimicrobial peptides, sequence-defined triazolium-grafted peptoid oligomers (6- to 12-mer) were designed to adopt an amphipathic helical polyproline I-type structure. Their evaluation on a panel of bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis), pathogenic fungi (Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus), and human cells (hRBC, BEAS-2B, Caco-2, HaCaT, and HepG2) enabled the identification of two heptamers with improved activity to selectively fight Staphylococcus aureus pathogens. Modulation of parameters such as the nature of the triazolium and hydrophobic/lipophilic side chains, the charge content, and the sequence length drastically potentiates activity and selectivity. Besides, the ability to block the proinflammatory effect induced by lipopolysaccharide or lipoteichoic acid was also explored. Finally, biophysical studies by circular dichroism and fluorescence spectroscopies strongly supported that the bactericidal effect of these triazolium-grafted oligomers was primarily due to the selective disruption of the bacterial membrane.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3915-3927"},"PeriodicalIF":4.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Preclinical Positron Emission Tomography (PET) of Prosthetic Joint Infection Using a Nitro-Prodrug of 2-[¹⁸F]F-p-Aminobenzoic Acid ([¹⁸F]F-PABA). 使用 2-[18F]F-p-Aminobenzoic Acid ([18F]F-PABA)硝基药物对假体关节感染进行临床前正电子发射断层扫描 (PET)。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-08 Epub Date: 2024-10-21 DOI: 10.1021/acsinfecdis.4c00075

Alyssa C Pollard-Kerning, Kaixuan Li, Yong Li, Shin Hye Ahn, Mingqian Wang, Melike Akoglu, Eduardo Bravo, Francesca DelloRusso, Hari K Akula, Wenchao Qu, Labros Meimetis, David J Schlyer, David E Komatsu, Peter J Tonge

{"title":"Preclinical Positron Emission Tomography (PET) of Prosthetic Joint Infection Using a Nitro-Prodrug of 2-[18F]F-p-Aminobenzoic Acid ([18F]F-PABA).","authors":"Alyssa C Pollard-Kerning, Kaixuan Li, Yong Li, Shin Hye Ahn, Mingqian Wang, Melike Akoglu, Eduardo Bravo, Francesca DelloRusso, Hari K Akula, Wenchao Qu, Labros Meimetis, David J Schlyer, David E Komatsu, Peter J Tonge","doi":"10.1021/acsinfecdis.4c00075","DOIUrl":"10.1021/acsinfecdis.4c00075","url":null,"abstract":"Deep-seated bacterial infections are difficult to detect and diagnose due to the lack of specific clinical imaging modalities. Therefore, the bacteria-specific positron emission tomography radiotracer 2-[18F]fluoro-4-nitrobenzoic acid ([18F]FNB) was developed, which is reduced to 2-[18F]fluoro-4-aminobenzoic acid ([18F]F-PABA) by bacterial nitroreductases and has improved pharmacokinetics compared to the parent compound. PET imaging demonstrated that the uptake of 2-[18F]fluoro-4-nitrobenzoic acid in a clinically relevant Staphylococcus aureus prosthetic joint infection model was up to ∼4-fold higher in the infected joint compared to the contralateral joint. 2-[18F]Fluoro-4-nitrobenzoic acid was also able to distinguish infection from inflammation in a surgical inflammation model. Based on the mouse radiation dosimetry results, the calculated effective dose of 2-[18F]fluoro-4-nitrobenzoic acid was well below the whole-body radiation dose limit established by the Food and Drug Administration for humans. In addition, no treatment-related microscopic changes in organ histopathology were observed in a mouse acute toxicity study. Overall, these data suggest that 2-[18F]fluoro-4-nitrobenzoic acid is a specific and effective imaging agent for noninvasively diagnosing prosthetic joint infections.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3765-3774"},"PeriodicalIF":4.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Antimicrobial Potency of Nor-Pyochelin Analogues and Their Cation Complexes against Multidrug-Resistant Pathogens. Nor-Pyochelin 类似物及其阳离子复合物对耐多药病原体的抗菌效力。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-08 Epub Date: 2024-10-29 DOI: 10.1021/acsinfecdis.4c00421

N G Hasitha Raviranga, Mubarak Ayinla, Harini A Perera, Yunchuan Qi, Mingdi Yan, Olof Ramström

{"title":"Antimicrobial Potency of Nor-Pyochelin Analogues and Their Cation Complexes against Multidrug-Resistant Pathogens.","authors":"N G Hasitha Raviranga, Mubarak Ayinla, Harini A Perera, Yunchuan Qi, Mingdi Yan, Olof Ramström","doi":"10.1021/acsinfecdis.4c00421","DOIUrl":"10.1021/acsinfecdis.4c00421","url":null,"abstract":"The opportunistic pathogen Pseudomonas aeruginosa develops increasing resistance toward even the most potent antibiotics. Like other bacteria, the pathogen produces a number of virulence factors including metallophores, which constitute an important group. Pseudomonads produce the iron-chelating metallophore (siderophore) pyochelin, which, in addition to its iron-scavenging ability, is an effector for the transcriptional regulator PchR in its FeIII-bound form (ferripyochelin). In the present study, docking studies predicted a major ferripyochelin binding site in PchR, which prompted the exploration of nor-pyochelin analogues to produce tight binding to PchR, and thereby upregulation of the pyochelin metabolism. In addition, we investigated the effects of using the analogues to bind the antimicrobial cations GaIII and InIII. Selected analogues of nor-pyochelin were synthesized, and their GaIII- and InIII-based complexes were assessed for antimicrobial activity. The results indicate that the GaIII complexes inhibit the pathogens under iron-limited conditions, while the InIII-based systems are more effective in iron-rich media. Several of the GaIII complexes were shown to be highly effective against a multidrug-resistant P. aeruginosa clinical isolate, with minimum inhibitory concentrations (MICs) of ≤1 μg/mL. Similarly, two of the InIII-based systems were particularly effective against the isolate, with an MIC of 8 μg/mL. These results show high promise in comparison with other, traditionally potent antibiotics, as the compounds generally indicated low cytotoxicity toward mammalian cells. Preliminary mechanistic investigations using pseudomonal transposon mutants suggested that the inhibitory effects of the InIII-based systems could be due to acute iron deficiency as a result of InIII-bound bacterioferritin.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3842-3852"},"PeriodicalIF":4.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

New Strides in Prevention of Malaria during Pregnancy Present Multitudinous Opportunities. 预防孕期疟疾的新进展带来了众多机遇。

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-08 Epub Date: 2024-10-15 DOI: 10.1021/acsinfecdis.4c00566

Jasmita Gill, Anupkumar R Anvikar

{"title":"New Strides in Prevention of Malaria during Pregnancy Present Multitudinous Opportunities.","authors":"Jasmita Gill, Anupkumar R Anvikar","doi":"10.1021/acsinfecdis.4c00566","DOIUrl":"10.1021/acsinfecdis.4c00566","url":null,"abstract":"Pregnant women are at a higher risk of developing complications from malaria, a mosquito-borne disease caused by Plasmodium parasites, resulting in considerable maternal and infant morbidity and mortality. Malaria in pregnancy causes unfavorable and life-threatening outcomes for both the mother and fetus not limited to maternal anemia, hypoglycaemia, cerebral malaria, pulmonary edema, and puerperal sepsis. WHO recommends wide-ranging strategies for this detrimental but preventable disease; however, numerous challenges persist in ensuring high uptake of preventive therapies, effective usage of insecticide-treated bed nets, and early initiation and optimal antenatal care coverage for pregnant women. This work distils recent global advances in preventive strategies for malaria in pregnancy. We discuss three mainstay interventions by WHO, viz. intermittent preventive treatment of malaria in pregnancy (IPTp), utilization and outcomes of insecticide-treated bed nets (ITNs), and headways in malaria case management using therapeutic drugs. We cover multitudinous facets of antenatal care, WHO-advised community-based delivery of IPTp (c-IPTp), intermittent screening and treatment for malaria in pregnancy (ISTp), a malaria vaccine for pregnant women, and auxiliary factors that are crucial for improving prevention outcomes. Despite the reduction in malaria globally, malaria in pregnancy remains a prevalent issue in endemic areas, which warrants strengthening of preventative strategies. This work attempts to consolidate pivotal observations of the prevention of malaria during pregnancy by highlighting key advances, priority areas, new opportunities, research gaps, and challenges that need to be addressed to ensure improved outcomes in pregnant women infected with malaria.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3721-3735"},"PeriodicalIF":4.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

UBR7 E3 Ligase Suppresses Interferon-β Mediated Immune Signaling by Targeting Sp110 in Hepatitis B Virus-Induced Hepatocellular Carcinoma. UBR7 E3连接酶通过靶向乙型肝炎病毒诱导的肝细胞癌中的Sp110抑制干扰素-β介导的免疫信号转导

IF 4 2区医学

ACS Infectious Diseases Pub Date : 2024-11-08 Epub Date: 2024-06-28 DOI: 10.1021/acsinfecdis.4c00213

Vipin Singh, Atanu Mondal, Santanu Adhikary, Payel Mondal, Niranjan Shirgaonkar, Ramanuj DasGupta, Siddhartha Roy, Chandrima Das

{"title":"UBR7 E3 Ligase Suppresses Interferon-β Mediated Immune Signaling by Targeting Sp110 in Hepatitis B Virus-Induced Hepatocellular Carcinoma.","authors":"Vipin Singh, Atanu Mondal, Santanu Adhikary, Payel Mondal, Niranjan Shirgaonkar, Ramanuj DasGupta, Siddhartha Roy, Chandrima Das","doi":"10.1021/acsinfecdis.4c00213","DOIUrl":"10.1021/acsinfecdis.4c00213","url":null,"abstract":"A newly discovered E3 ubiquitin ligase, UBR7, plays a crucial role in histone H2BK120 monoubiquitination. Here, we report a novel function of UBR7 in promoting hepatitis B virus (HBV) pathogenesis, which further leads to HBV-induced hepatocellular carcinoma (HCC). Transcriptomics analysis from HCC patients revealed the deregulation of UBR7 in cancer. Remarkably, targeting UBR7, particularly its catalytic function, led to a significant decrease in viral copy numbers. We also identified the speckled family protein Sp110 as an important substrate of UBR7. Notably, Sp110 has been previously shown to be a resident of promyelocytic leukemia nuclear bodies (PML-NBs), where it remains SUMOylated, and during HBV infection, it undergoes deSUMOylation and exits the PML body. We observed that UBR7 ubiquitinates Sp110 at critical residues within its SAND domain. Sp110 ubiquitination downregulates genes in the type I interferon response pathway. Comparative analysis of RNA-Seq from the UBR7/Sp110 knockdown data set confirmed that the IFN-β signaling pathway gets deregulated in HCC cells in the presence of HBV. Single-cell RNA-Seq analysis of patient samples further confirmed the inverse correlation between the expression of Sp110/UBR7 and the inflammation score. Notably, silencing of UBR7 induces IRF7 phosphorylation, thereby augmenting interferon (IFN)-β and the downstream interferon-stimulated genes (ISGs). Further, wild-type but not the ubiquitination-defective mutant of Sp110 could be recruited to the type I interferon response pathway genes. Our study establishes a new function of UBR7 in non-histone protein ubiquitination, promoting viral persistence, and has important implications for the development of therapeutic strategies targeting HBV-induced HCC.","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":" ","pages":"3775-3796"},"PeriodicalIF":4.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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