{"title":"miR-186 Regulates Septic Hyperinflammation and Predicts Sepsis","authors":"Xiangru Li, Hongyan Cai, Boyuan Wang, Weiwei Luo, Rui Jia, Shaoyan Si, Mei Hu, Xiaotong Lou","doi":"10.1111/1348-0421.70007","DOIUrl":"10.1111/1348-0421.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis is a life-threatening condition caused by infection-induced immune dysregulation. Clinically distinguishing sepsis from infection remains to be a challenge due to overlapping clinical features. Although miR-186 regulates cell proliferation and apoptosis, and was predicted to target immune-related genes, its role in sepsis is unclear. We retrospectively enrolled 21 infected patients and 20 sepsis patients. The miR-186 level in blood cells was detected using real-time PCR. Cytokine concentrations and lymphocyte subpopulation proportions were determined using flow cytometry. Clinical data were retrieved from medical records. The diagnostic ability of miR-186 was compared with procalcitonin and lactate using the receiver operating characteristic (ROC) curve. miR-186 was inhibited in human umbilical vein endothelial cells (HUVECs) and mice, followed by measurement of cytokine expression using real-time PCR and flow cytometry. The expression level of miR-186 was significantly higher in septic patients than in infected patients. miR-186 showed relatively better diagnostic performance for sepsis than procalcitonin and lactate. The in vitro assay showed that LPS enhanced miR-186 expression under a dose-dependent manner. In vitro miR-186 inhibition in HUVECs inhibited <i>IL-1β</i>, <i>IL-6</i>, and <i>IL-8</i> expression. In vivo miR-186 inhibition significantly lowered IL-1β concentration and natural killer cell ratio. In this study, we found that miR-186 is significantly upregulated in sepsis and plays a regulatory role in cytokine expression, highlighting its potential as a diagnostic biomarker for sepsis.</p></div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 10","pages":"522-531"},"PeriodicalIF":1.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144794861","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":"Screening and Characterization of B-Cell Epitopes of Porcine Respiratory Coronavirus Receptor Binding Domain Using Monoclonal Antibodies","authors":"Aiping Wang, Jiachen Wang, Jingming Zhou, Yumei Chen, Hongliang Liu, Chao Liang, Xifang Zhu, Enping Liu, Sixuan Wu, Yanhua Qi, Gaiping Zhang","doi":"10.1111/1348-0421.70002","DOIUrl":"10.1111/1348-0421.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>The spike (S) glycoprotein of porcine respiratory coronavirus (PRCV) plays a critical role in viral entry, with its receptor binding domain (RBD) on the S1 subunit responsible for interacting with the host receptor porcine aminopeptidase N. In this study, the PRCV RBD protein was successfully expressed, and a monoclonal antibody (mAb), 2E6, was produced using hybridoma technology. The specificity of 2E6 was confirmed by western blot and indirect immunofluorescence assay (IFA). To identify the linear B-cell epitope recognized by 2E6, the RBD was initially divided into three overlapping fragments, cloned into pET-32a vectors, and expressed in <i>Escherichia coli</i> BL21 (DE3). Dot blot analysis revealed that 2E6 reacted with the RBD-1 fragment (amino acids 299–357). Further subdivision into RBD1-1, RBD1-2, and RBD1-3, followed by expression using both pET-32a and pEGFP-C1 vectors, enabled Dot blot and IFA validation of specific recognition of RBD1–3 (amino acids 329–347). Subsequent peptide mapping using synthetic overlapping peptides (RBD-P1, P2, P3) confirmed that the minimal linear epitope lies within RBD-P2 (amino acids 334–343). This epitope is surface-exposed and conserved among PRCV strains, making it a promising candidate for diagnostic assay development and epitope-based vaccine design.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 9","pages":"477-485"},"PeriodicalIF":1.8,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768784","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}
Hiroki Kondo, Juri Koizumi, Keita Takahashi, Tetsuo Koshizuka
{"title":"Evaluation of the Antiherpes Simplex Virus Activities of Thiourea-Based Compounds","authors":"Hiroki Kondo, Juri Koizumi, Keita Takahashi, Tetsuo Koshizuka","doi":"10.1111/1348-0421.70005","DOIUrl":"10.1111/1348-0421.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>The emergence of drug-resistant viruses, particularly in immunocompromised individuals, has necessitated the development of novel antiviral drugs. We previously identified compound 147B3 as an inhibitor of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). Although 147B3 exhibits cytotoxicity, it inhibits the function of infected cell protein 4 (ICP4), a viral transcription factor essential for HSV-1 replication. In this study, we evaluated five commercially available compounds (1C6, 1C6L, 1H6, 1H6L, and 2D10) that had structural similarity to 147B3, exhibited potent anti-HSV-1 activity with reduced cytotoxicity. Among these, 1C6L and 1H6L are structural analogs of 1C6 and 1H6, respectively. An HSV-1 strain resistant to 147B3 carrying a mutation in ICP4 exhibited resistance to all the five compounds, suggesting a shared mechanism of action involving ICP4. Among these compounds, 1H6L had the highest selective index against HSV-1. Notably, these compounds did not reduce early or late protein expression of HSV-1, unlike the parent compound 147B3. Although viral genome replication occurred in the presence of 1H6L, it prevented virion release into the culture supernatant. The cell fraction analysis revealed that 1H6L reduced the size of the cytoplasmic HSV-1 genome. These findings suggest that 1H6L shares certain aspects of its mechanism of action with the parent compound 147B3 but may also inhibit multiple steps in the HSV-1 life cycle.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 10","pages":"511-521"},"PeriodicalIF":1.8,"publicationDate":"2025-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144768783","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}
Aila Gulijiahani, Vuk Isakovic, Yasuko Mori, Jun Arii
{"title":"Comparative Analysis of the Nuclear Egress Complex in Human Herpesvirus 6A and 6B","authors":"Aila Gulijiahani, Vuk Isakovic, Yasuko Mori, Jun Arii","doi":"10.1111/1348-0421.70004","DOIUrl":"10.1111/1348-0421.70004","url":null,"abstract":"<div>\u0000 \u0000 <p>Herpesvirus nucleocapsids are transported from the nucleus to the cytoplasm via a conserved process known as nuclear egress, which is mediated by the nuclear egress complex (NEC) consisting of two core viral proteins. Although the NEC structure is conserved among herpesviruses, functional divergence may exist. Human herpesvirus 6A (HHV-6A) and HHV-6B are genetically similar members of the <i>Roseolovirus</i> genus within the <i>Betaherpesvirinae</i> subfamily, yet they differ in their pathogenic profiles. In this study, we examined and compared the functions of NEC components U37 and U34 from HHV-6A and HHV-6B. We demonstrated that HHV-6A U34 localizes to the nuclear envelope via its C-terminal transmembrane domain and is essential for viral replication. Moreover, NEC components from HHV-6A and HHV-6B colocalize at the nuclear rim and share a high degree of sequence similarity. These findings suggest that the nuclear egress mechanism is highly conserved within roseoloviruses, despite their distinct biological properties.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 10","pages":"502-510"},"PeriodicalIF":1.8,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718170","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}
Karin C. Garcia, Samuel N. Santos, Bruna R. Flose, Maria A. Juliano, Renan B. Domingues, Lucas M. Neves, Guilherme José Costa Silva, Liã B. Arruda, Augusto C. Penalva-de-Oliveira, Sandro L. de Andrade Matas, Marina T. Shio, Luiz H. da Silva Nali
{"title":"Anti-Human Endogenous Retrovirus and Anti-Myelin Oligodendrocyte Glycoprotein Humoral Response in Cerebrospinal Fluid of Multiple Sclerosis Patients: A Case Control Study","authors":"Karin C. Garcia, Samuel N. Santos, Bruna R. Flose, Maria A. Juliano, Renan B. Domingues, Lucas M. Neves, Guilherme José Costa Silva, Liã B. Arruda, Augusto C. Penalva-de-Oliveira, Sandro L. de Andrade Matas, Marina T. Shio, Luiz H. da Silva Nali","doi":"10.1111/1348-0421.70003","DOIUrl":"10.1111/1348-0421.70003","url":null,"abstract":"<p>It is believed that human endogenous retrovirus (HERV)-W plays a fundamental role in multiple sclerosis (MS) pathogenesis, probably by inducing humoral and cellular immunopathological response. HERVs present regions of similarity to myelin oligodendrocyte glycoprotein (MOG) and therefore could induce autoimmunity through the mechanism of molecular mimicry via cross-humoral response. This study aimed to evaluate the impact of HERV-mediated humoral response among MS patients by assessing IgG antibody levels of HERV-W and K in cerebrospinal fluid (CSF). CSF samples were collected from MS patients (<i>n</i> = 25) and idiopathic intracranial hypertension (IIH) patients (<i>n</i> = 25). Serum samples from MS group (<i>n</i> = 25) were also analyzed. CSF samples were assessed for global and differential cell counts, analytical biochemistry, and oligoclonal bands analysis. ELISA was used to determine the serum and intrathecal (CSF) presence and concentration of anti-MOG, anti-HERV-W-env, and anti-HERV-K-pol antibodies. ELISA findings revealed higher concentrations of anti-MOG and HERV-W IgG in MS compared to IIH (<i>p</i> < 0.01 and <i>p</i> = 0.0142 respectively), while HERV-K IgG showed concentration to three HERV-K peptides (<i>p</i> < 0.01). A positive correlation was also observed between serum and CSF antibody concentration for MOG (<i>r</i> = 0.47 <i>p</i> = 0.01), HERV-W (<i>r</i> = 0.72 <i>p</i> < 0.01), and three HERV-K peptides (<i>r</i> = 0.49, 0.57, 0.61 and <i>p</i> = 0.0126, <i>p</i> < 0.01, and <i>p</i> < 0.01, respectively) among MS patients. Our findings revealed high concentrations of anti-HERV-K and -W antibodies in serum and CSF among MS patients, suggesting a possible role of humoral immunopathological response. In addition, the positive correlation between serum and CSF antibody concentration indicates the potential application of serum levels of anti-HERV and anti-MOG as biomarkers for MS.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 10","pages":"495-501"},"PeriodicalIF":1.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144690980","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":"Therapeutic Potential of Lactobacillus plantarum ATG-K2 in Bacterial Vaginosis: In Vitro and In Vivo Evidence","authors":"Yeon-Hwa Park, Juyi Park, Ye-Won Kang, Jihee Kang","doi":"10.1111/1348-0421.70001","DOIUrl":"10.1111/1348-0421.70001","url":null,"abstract":"<div>\u0000 \u0000 <p>Bacterial vaginosis (BV) is characterized by reduced vaginal lactobacilli and pathogenic bacteria proliferation, leading to symptoms such as vaginal epithelial cell detachment and unpleasant odor, along with various complications. Most <i>Lactobacillus</i> species play a crucial role in not only inhibiting BV, but also maintaining vaginal health. We aimed to determine whether <i>Lactobacillus plantarum</i> ATG-K2 has therapeutic and preventive effects against <i>Gardnerella vaginalis</i> (GV), a representative pathogen of BV. In vitro cell assays confirmed that ATG-K2 clusters within cells without cytotoxic effects and inhibits both the cytotoxicity and GV adhesion. Furthermore, biofilm formation assays using crystal violet revealed that ATG-K2 disrupts GV-formed biofilms. In GV-induced BV mouse models, ATG-K2 reduced clue cell formation and sialidase activity, thereby addressing the key aspects of BV. Additionally, when ATG-K2 was administered, the measurement of GV DNA within the vaginal tissue revealed a reduction in GV. In conclusion, ATG-K2 holds promise as a therapeutic agent for BV by inhibiting GV colonization and the associated pathology, potentially offering an alternative to antibiotics.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 9","pages":"457-465"},"PeriodicalIF":1.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659630","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":"Functional Rewiring of Three Pneumococcal Proteins Into Plasminogen Binders","authors":"Yoshihito Yasui, Satoru Hirayama, Hisanori Domon, Koichi Tabeta, Yutaka Terao","doi":"10.1111/1348-0421.70000","DOIUrl":"10.1111/1348-0421.70000","url":null,"abstract":"<div>\u0000 \u0000 <p>To investigate the mechanisms underlying pneumococcal infection, a proteomic analysis was previously conducted to identify pneumococcal proteins in infected mouse samples. In the present study, we characterized three proteins, ATP synthase subunit beta (AtpD), ABC transporter transmembrane protein (Vex3), and fructose bisphosphate aldolase (Fba), which bind to human plasminogen and subsequently facilitate its conversion to plasmin by tissue-type plasminogen activator. These findings suggest that <i>Streptococcus pneumoniae</i> might exploit the proteolytic activity of plasmin to promote infection and highlights the potential importance of plasminogen-binding capacity in the pathogenesis of pneumococcal infection.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 9","pages":"486-492"},"PeriodicalIF":1.8,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626623","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}
M. Ishrat Jahan, Toshiaki Inenaga, Sakurako Makimoto, Md. Belal Hossain, Yuka Matsuoka, Sharmin Nahar Sithi, Samiul Alam Rajib, Arif Nur Muhammad Ansori, Kenji Sugata, Kazuhiko Imakawa, Tomoko Kobayashi, Yorifumi Satou
{"title":"Circulating Cell-Free DNA of Bovine Leukemia Virus: A Promising Biomarker for Enzootic Bovine Leukosis","authors":"M. Ishrat Jahan, Toshiaki Inenaga, Sakurako Makimoto, Md. Belal Hossain, Yuka Matsuoka, Sharmin Nahar Sithi, Samiul Alam Rajib, Arif Nur Muhammad Ansori, Kenji Sugata, Kazuhiko Imakawa, Tomoko Kobayashi, Yorifumi Satou","doi":"10.1111/1348-0421.13231","DOIUrl":"10.1111/1348-0421.13231","url":null,"abstract":"<p>Bovine leukemia virus (BLV) causes Enzootic bovine leukosis (EBL) in approximately 1%–5% of infected cattle after a long latent period. Few biomarkers effectively distinguish non-EBL from EBL cattle. Given the rapid turnover of tumor cells, we hypothesized that cell-free DNA (cfDNA) in plasma could serve as a more effective biomarker for EBL diagnosis. We measured the proviral load (PVL) in whole blood and plasma by quantitative PCR targeting LTR and <i>pol</i>. Consistent with previous reports, PVL levels in whole blood in EBL cattle were generally higher than those in non-EBL with some overlap between these two groups. In contrast, PVL in plasma clearly distinguished non-EBL from EBL ones. The receiver operating characteristic analysis showed plasma PVL perfectly discriminated EBL from non-EBL (100% sensitivity and specificity), while whole-blood PVL achieved 70% sensitivity and 30% specificity. Additionally, length of PCR products played a role in PVL detection sensitivity in plasma. We compared the complete BLV sequence between genomic DNA from lymphoma tissue and cfDNA in plasma and found that the predominant BLV sequences were highly similar between them. By assessing the major tumor clone burden based on unique integration sites, we found that BLV cfDNA derived more from tumor clones in the tissues than from peripheral blood mononuclear cells (PBMCs). These data support the idea that BLV in cfDNA primarily originates from tumor cells in EBL cattle. These findings demonstrated that cfDNA could be a better indicator for EBL diagnosis, improving early detection and more timely intervention to reduce the economic loss in the meat and dairy industry.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"69 9","pages":"466-476"},"PeriodicalIF":1.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13231","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575894","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":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.13143","DOIUrl":"https://doi.org/10.1111/1348-0421.13143","url":null,"abstract":"<p><b>Cover photograph</b>: The three pillars of horizontal gene transfer of ARGs. (1) Conjugation. ARG-carrying plasmids with self-transmissibility are transferred from donor cells to recipient cells upon cell-to-cell contact. As a result, identical plasmids are ultimately present in both donor and recipient cells. (2) Transformation. DNA fragments carrying ARGs, released upon donor cell death, are taken up by recipient cells and integrated into their chromosomes via homologous recombination. (3-1) Specialized transduction. Phage particles containing structural genes and accessory ARGs are released from donor cells and attach to recipient cells. The phage structural genes and accessory ARGs are then injected into the recipient cells, and they are subsequently integrated into the recipient's chromosome. (3-2) Generalized transduction. Phage particles containing host cell DNA, including ARGs, are released from donor cells and attach to recipient cells. The donor-derived genes including ARGs are then injected into the recipient cells and subsequently integrated into the recipient's chromosome. <i>Microbiol Immunol: 69:367-376</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 7","pages":"i-ii"},"PeriodicalIF":1.9,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.13143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551139","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}