Microbiology and Immunology最新文献

{"title":"METTL3 Promotes Oxidative Stress and Inflammation in Myoblasts During Chronic Kidney Disease Related Sarcopenia Through the TLR4 NF-κB Pathway.","authors":"Qiong Wu, Qin Zou, Shenghai Long, Hua Deng, Yi Cui","doi":"10.1111/1348-0421.70014","DOIUrl":"https://doi.org/10.1111/1348-0421.70014","url":null,"abstract":"<p><p>Chronic kidney disease (CKD)-related sarcopenia is a debilitating complication characterized by progressive skeletal muscle loss, primarily driven by oxidative stress and inflammation. However, the molecular mechanisms underlying this condition are still not fully clarified. This study aimed to investigate the role of N6-methyladenosine (m⁶A) Methyltransferase-Like 3 (METTL3) in mediating oxidative stress and inflammation through the TLR4/NF-κB signaling pathway in the context of CKD-associated muscle atrophy. C2C12 myoblasts were treated with Indoxyl Sulfate (IS) to mimic the uremic environment of CKD.METTL3 expression was silenced via shRNA, and lipopolysaccharide (LPS) was used to activate TLR4/NF-κB signaling. Proinflammatory cytokines, oxidative stress levels, and Myogenic differentiation markers were measured using qRT-PCR, Western blot analysis, enzyme-linked immunosorbent assay (ELISA), and reactive oxygen species (ROS) assays. The interaction between METTL3 and Toll-like receptor 4(TLR4) mRNA was confirmed by methylated RNA immunoprecipitation (MeRIP). A CKD rat model was established via 5/6 nephrectomy, followed by in vivo METTL3 silencing using AAV-shRNA to assess muscle atrophy and renal function. METTL3 was significantly upregulated in IS-treated myoblasts and CKD rat muscle tissue. Knockdown of METTL3 restored myogenic differentiation, reduced ROS and malondialdehyde levels, increased glutathione (GSH) content, and suppressed the expression of TNF-α, IL-6, and IL-1β. MeRIP analysis confirmed m⁶A modification of TLR4 mRNA mediated by METTL3, which enhanced TLR4 expression and downstream NF-κB activation. METTL3 silencing in CKD rats improved muscle histology, reduced systemic inflammation, and partially restored renal function. METTL3 promotes oxidative stress, inflammation, and skeletal muscle atrophy in CKD-associated sarcopenia by enhancing TLR4/NF-κB signaling via m⁶A modification. These findings identify METTL3 as a potential therapeutic target for ameliorating sarcopenia in CKD.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First Versatile Reverse Genetics System for DNA Viruses Using Circular Polymerase Extension Reaction.","authors":"Hirotaka Yamamoto, Tomokazu Tamura, Rigel Suzuki, Saori Suzuki, Takasuke Fukuhara","doi":"10.1111/1348-0421.70016","DOIUrl":"https://doi.org/10.1111/1348-0421.70016","url":null,"abstract":"<p><p>Reverse genetics enables the generation of recombinant viruses; however, conventional approaches using full-length cDNA cloned into bacterial artificial chromosomes or plasmids are time-consuming and technically challenging. While the circular polymerase extension reaction (CPER) has been applied to RNA viruses, it has not been used for DNA viruses. Here, we successfully applied CPER to generate infectious recombinant adenoviruses (AdVs) of two serotypes. The resulting viruses replicated comparably to parental strains, and replication was confirmed by immunostaining. These findings demonstrate that CPER is a rapid and efficient platform for reverse genetics of DNA viruses and may accelerate AdV research and therapeutic development.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Actinobacillus pleuropneumoniae: An Update on Epidemiology, Biovar, Serotyping, Virulence, and Laboratory Diagnosis.","authors":"Ho To, Joachim Frey, Marcelo Gottschalk, Katsuaki Sugiura, Shinya Nagai","doi":"10.1111/1348-0421.70017","DOIUrl":"https://doi.org/10.1111/1348-0421.70017","url":null,"abstract":"<p><p>Actinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia, a highly contagious respiratory disease. It is classified into two biovars on the basis of NAD requirement for growth: biovar 1 (NAD-dependent) and biovar 2 (NAD-independent). Biovar 1 consists of 17 serovars (1-12 and 15-19) and biovar 2 has 8 serovars (2, 4, 7, 9, 11, 13, 14, and 17). Several virulence factors are responsible for the pathogenesis of A. pleuropneumoniae, particularly Apx toxins, capsular polysaccharides, lipopolysaccharides, and membrane proteins. In this review, the current knowledge of biovars, serovars, epidemiology, virulence factors of A. pleuropneumoniae as well as laboratory diagnosis and vaccines are summarized.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a Multiple Epitopes-Based Dengue Vaccine: An Immunoinformatics Approach and Insights From Pakistani Population Genetics.","authors":"Ali Hassan, Malik Siddique Mahmood, Muhammad Idrees, Samia Afzal","doi":"10.1111/1348-0421.70015","DOIUrl":"https://doi.org/10.1111/1348-0421.70015","url":null,"abstract":"<p><p>Dengue fever poses a grave threat to public health worldwide, claiming numerous fatalities each year with tropical regions being particularly hard hit by dengue outbreaks. The multiple-epitope construct is tailored to the dengue virus's geographical prevalence and the genetics of the Pakistani population. 14 experimentally validated MHC-I and MHC-II epitope sequences, were employed to generate the variants by taking into account the conservancy in all serotypes. Subsequently, the binding affinities of each derived variant against the human leukocyte antigen alleles most common among the Pakistani population were analyzed. A total of three epitopes, two Class-I (GTSGSPIINR and RSWNTGFDW), and one Class-II (ILAPTRVVAAEMEEA), with a combined Pakistani population coverage of more than 73%, together with five linear B cell epitopes were used to create six possible multi-epitope fusion constructs. The molecular docking analysis indicated that two constructs demonstrated notable binding affinities for the most abundant HLA-A*11:01 in Pakistan. Additionally, molecular dynamics (MD) simulations identified one of the constructs as a promising therapeutic candidate. The vaccine construct selected from this analysis could aid in future vaccine design for the dengue virus following further in vitro test validation and in vivo studies to investigate its immune protection capacity.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Hepatitis C Virus Genotype 3a S310 Strain Permits Claudin-1-Independent Entry.","authors":"Ryosuke Suzuki, Keigo Yato, Takashi Tosaka, Mami Matsuda, Su Su Hmwe, Masayoshi Fukasawa, Takasuke Fukuhara, Yoshiharu Matsuura, Masamichi Muramatsu, Takaji Wakita","doi":"10.1111/1348-0421.70013","DOIUrl":"https://doi.org/10.1111/1348-0421.70013","url":null,"abstract":"<p><p>We investigated the receptor usage of the hepatitis C virus (HCV) genotype 3a S310 strain using cell culture-derived HCV (HCVcc) and trans-complemented HCV particles (HCVtcp). Infection by HCV strains of genotypes 1, 2, and 3 was inhibited by anti-CD81 antibody. By contrast, anti-claudin (CLDN)1 antibody reduced infection by the genotype 1b TH strain and genotype 2a JFH-1 strain but had no effect on the S310 strain (genotype 3a). Moreover, CLDN1-knockout cells remained permissive to infection with a chimeric HCVcc bearing the S310 envelope in a JFH-1 backbone. In CLDN1-deficient cells, infection by HCVtcp derived from the S310 strain was significantly reduced by treatment with anti-claudin-6 (CLDN6) antibody or knockdown of CLDN6 mRNA, suggesting that the S310 strain utilizes CLDN6 as an alternate entry factor. Further analyses revealed that HCVtcp of genotype 4a (ED43 strain) and genotype 6a (HK6a strain) also infected CLDN1-deficient cells. These findings provide new insights into CLDN usage by diverse HCV genotypes and raise the possibility that CLDN tropism may affect viral entry, infection efficiency, and pathogenesis.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145239247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.70011","DOIUrl":"https://doi.org/10.1111/1348-0421.70011","url":null,"abstract":"<p><b>Cover photograph</b>: Co-localization of NEC components from HHV-6A and HHV-6B. HEK293T cells were co-transfected with the indicated combinations of plasmids encoding NEC components from HHV-6A or HHV-6B. After 48 hours, the cells were fixed, stained with antibodies specific for the Strep and Flag tags and analyzed by confocal microscopy. Scale bar, 10 μm. <i>Microbiol Immunol: 69:502-510</i>. Article link here\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 10","pages":"i-ii"},"PeriodicalIF":1.8,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular and Functional Characterization of Sika Deer ACE2 as a Receptor for SARS-CoV-2.","authors":"Anastasiia Kovba, Manabu Igarashi, Keita Mizuma, Yuma Ohari, Manabu Onuma, Michito Shimozuru, Kotaro Shimizu, Masami Yamanaka, Keita Matsuno, Toshio Tsubota","doi":"10.1111/1348-0421.70012","DOIUrl":"https://doi.org/10.1111/1348-0421.70012","url":null,"abstract":"<p><p>Surveillance of SARS-CoV-2 in white-tailed deer (WTD, Odocoileus virginianus) has revealed its widespread and sustained transmission across North America, with evidence suggesting possible transmission from deer to humans. In the following surveillance studies in other deer species, however, little evidence of infection spread was found, including in sika deer (Cervus nippon) in our previous study. Differences in the structure of the virus entry receptor angiotensin-converting enzyme 2 (ACE2) are known to act as one of the functional barriers to SARS-CoV-2 infection. To investigate the molecular basis of the lack of SARS-CoV-2 transmission to sika deer, we performed structural and functional analyses of the sika deer ACE2 in comparison with WTD ACE2. Comparison of sika deer ACE2 sequence and those of cervid species with WTD ACE2, followed by in silico molecular dynamics analysis, revealed a substitution of lysine to asparagine in position 31 commonly found in cervid ACE2s can potentially alter binding to the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD). Functional assays in cells expressing sika deer and WTD ACE2s showed minimal differences in viral binding and replication, demonstrating that SARS-CoV-2 can similarly utilize ACE2 from both species. These findings suggest that sika deer and possibly other cervids may be highly susceptible to SARS-CoV-2 and highlight the need to investigate other factors impacting virus spread in deer populations.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification and Functional Analysis of Key Genes Involved in Community-Acquired Pneumonia Inflammation Based on Bioinformatics.","authors":"Chao Li, Zhidan Hua, Xiaoling Wang, Suqin Wen, Jianhui Sheng","doi":"10.1111/1348-0421.70010","DOIUrl":"https://doi.org/10.1111/1348-0421.70010","url":null,"abstract":"<p><p>Previous studies have revealed various treatment modalities for community-acquired pneumonia (CAP), but there is still a lack of in-depth research on inflammation-related genes (IRGs) in CAP. In this analysis, we collected clinical data from CAP patients and identified CAP differentially expressed IRGs (CAP-DE-IRGs) between healthy individuals and CAP patients. Subsequently, functional and pathway enrichment analyses were carried out on CAP-DE-IRGs. Furthermore, hub genes in IRGs were identified, with their diagnostic ability and function validated. Enrichment analyses demonstrated that these CAP-DE-IRGs were abundant in biological processes such as cytokine-cytokine receptor interaction and JAK-STAT signaling pathway. Five hub genes were selected from IRGs. Quantitative Real-time PCR (qRT-PCR) results showed that CCL5, IL7R, IL2RB, and IL10RA were significantly downregulated in CAP patients, and IL18R1 was significantly upregulated in CAP patients (p < 0.05). In the validation of the diagnostic ability of hub genes, most of the genes exhibited area under curve (AUC) values exceeding 0.7, indicating the excellent diagnostic ability of hub genes. The function prediction of hub genes unraveled that hub genes had the functions of cytokine receptor binding, immune receptor activity, response to interleukin-7, and so on. The immune infiltration analysis demonstrated that immune cell Neutrophils exhibited higher infiltration in CAP patients than in healthy individuals. The correlation analysis of hub genes and CAP-related genes manifested that the hub gene IL18R1 was positively correlated with CAP-related genes. In summary, our analysis identified a connection between CAP patients and IRGs, which is beneficial for further research on CAP.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.70009","DOIUrl":"https://doi.org/10.1111/1348-0421.70009","url":null,"abstract":"<p><b>Cover photograph</b>: Spatial localisation of epitope regions. <i>Microbiol Immunol: 69:477–485</i>. Article link here\u0000 \u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 9","pages":"i-ii"},"PeriodicalIF":1.8,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enterotoxigenic Escherichia coli Vaccine Candidate MecVax With Protein Antigens Prepared From Animal-Free Media Is Equally Immunogenic and Protective Against Adhesins CFA/I, CS1-CS6 and Toxins LT and STa.","authors":"Ipshita Upadhyay, Bedaso Edao, Weiping Zhang","doi":"10.1111/1348-0421.70008","DOIUrl":"10.1111/1348-0421.70008","url":null,"abstract":"<p><p>Enterotoxigenic Escherichia coli (ETEC) is a leading cause of diarrhea in young children in low- and middle-income countries and the most common cause of diarrhea in international travelers. Currently, there are no vaccines licensed to prevent ETEC-associated diarrhea. MecVax, a protein-based, multivalent ETEC vaccine candidate, has been demonstrated to be broadly immunogenic and cross-protective in preclinical studies. However, the two recombinant proteins of MecVax were prepared from 2× Yeast Extract Tryptone medium (2× YT, which contains animal materials) and are therefore unsuitable for a human vaccine. In this study, we prepared MecVax recombinant proteins using two animal material-free media (Terrific Broth Complete with animal-free Soytone and 2× YT with animal-free Soytone) and comparatively evaluated the vaccine products for immunogenicity and antibody functions against ETEC bacterial adherence and toxin enterotoxicity. Data showed that MecVax protein antigens prepared from a culture medium without or with animal materials showed no differences in protein yield, reactivity with specific antibodies, and induction of antigen-specific IgG responses in mice. Moreover, the mouse serum antibodies exhibited the same level of inhibition of adherence from ETEC bacteria expressing CFA/I, CS1-CS6, as well as neutralization of ETEC heat-stable toxin or heat-labile toxin. These results indicate that MecVax can be prepared using an animal-free Soytone medium, thereby accelerating the development of this vaccine product against ETEC-associated diarrhea in children and travelers. Additionally, we conducted an additional MecVax dosage study in mouse immunization and refined the minimum effective dose to 2 μg of each protein antigen.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}