{"title":"Issue Information – Cover","authors":"","doi":"10.1111/1348-0421.70087","DOIUrl":"https://doi.org/10.1111/1348-0421.70087","url":null,"abstract":"<p><b>Cover photograph</b>: Schematic illustration of the mAb-Fab competition assay. Immobilized IgG antibodies were loaded onto biosensors, followed by binding of purified HHV-6B tetramer in the presence or absence of competing Fab fragments. <i>Microbiol Immunol: 70:448-461.</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":"70 9","pages":"i-ii"},"PeriodicalIF":1.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1348-0421.70087","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904052","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":"Infection-Dependent Modulation of the Host Adaptor Gab2 During Chlamydia trachomatis Intracellular Development","authors":"Sora Kuroiwa, Taiki Deguchi, Torahiko Okubo, Shinji Nakamura, Hideaki Higashi, Hiroyuki Yamaguchi","doi":"10.1111/1348-0421.70064","DOIUrl":"10.1111/1348-0421.70064","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Chlamydia trachomatis</i> (Ct) is an obligate intracellular bacterium that can cause severe reproductive complications, including infertility and pelvic inflammatory disease. Its pathogenicity depends on intracellular maturation, which involves differentiation between infectious elementary (EB) and replicative reticulate bodies within inclusion vacuoles. Ct is known to modulate host PI3K-AKT signaling during this process; however, the molecular basis of this regulation remains unclear. To elucidate this mechanism, we screened host factors linked to the PI3K-AKT axis using a PI3K-AKT-mTOR compound library comprising 319 inhibitors, and identified the adaptor protein Gab2 (GRB2-associated binding protein 2) as a new target molecule of Ct. Gab2 protein levels decreased during the late phase of infection, and Gab2 silencing impaired intracellular replication without affecting EB formation. These findings demonstrate that Ct infection modulates the host adaptor Gab2 during intracellular development and provide new insights into host–pathogen interactions underlying chlamydial maturation.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 9","pages":"393-401"},"PeriodicalIF":1.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368912","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}
Zihan Xu, Chieko Matsui, Maria Alethea Septianastiti, Fransisca Puspitasari, Lin Deng, Takayuki Abe, Ikuo Shoji
{"title":"Hepatitis C Virus Enhances Lysosome-Associated Membrane Protein 2 A Transcription Through Nuclear Factor Erythroid 2-Related Factor 2 to Support Viral Replication","authors":"Zihan Xu, Chieko Matsui, Maria Alethea Septianastiti, Fransisca Puspitasari, Lin Deng, Takayuki Abe, Ikuo Shoji","doi":"10.1111/1348-0421.70077","DOIUrl":"10.1111/1348-0421.70077","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatitis C virus (HCV) establishes persistent infection by rewiring host stress-response pathways. Chaperone-mediated autophagy (CMA) contributes to HCV replication, but it remains unclear whether HCV regulates lysosome-associated membrane protein 2 A (LAMP-2A), the rate-limiting receptor for CMA. Here, we examined LAMP-2A regulation in HCV-infected Huh-7.5 cells. HCV infection increased LAMP-2A promoter activity, mRNA, and protein abundance, indicating transcriptional upregulation. Among candidate stress-responsive transcription factors, nuclear factor erythroid 2-related factor 2 (NRF2), hypoxia-inducible factor 1α (HIF-1α), and nuclear factor of activated T cells 1 (NFAT1) were elevated in infected cells. However, promoter mutagenesis identified NRF2 as the principal direct regulator. Mutation of the NRF2-responsive antioxidant response element markedly reduced basal and HCV-induced LAMP-2A promoter activity. Chromatin immunoprecipitation assays revealed NRF2 association with the LAMP-2A promoter, and HCV infection increased nuclear accumulation and Ser40 phosphorylation of NRF2. Functionally, shRNA-mediated knockdown of LAMP-2A reduced intracellular HCV RNA and protein levels. These findings identify an NRF2-LAMP-2A regulatory axis engaged during HCV infection and support a model in which HCV upregulates LAMP-2A to establish a cellular environment favorable for viral replication.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 9","pages":"462-473"},"PeriodicalIF":1.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520725","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}
Jacob Fadipe, Tomotaka Okamura, Shige H Yoshimura, Akatsuki Saito
{"title":"Naturally Occurring ZCCHC3 Variants Modulate Antiretroviral Activity in Cynomolgus Macaques.","authors":"Jacob Fadipe, Tomotaka Okamura, Shige H Yoshimura, Akatsuki Saito","doi":"10.1111/1348-0421.70088","DOIUrl":"https://doi.org/10.1111/1348-0421.70088","url":null,"abstract":"<p><p>Many mammalian cells restrict viral replication by utilizing various host restriction factors. We recently demonstrated that CCHC-type zinc-finger-containing protein 3 (ZCCHC3) suppresses human immunodeficiency virus type 1 (HIV-1) replication through multiple mechanisms. We also revealed that single-nucleotide polymorphisms in human ZCCHC3 affect its antiviral function; however, whether similar genetic and functional diversity is present in other species remains unknown. In this study, we investigated the genetic and functional diversity of ZCCHC3 in cynomolgus macaques, a critical animal model for HIV-1-related research. Sequencing analysis of eight independent ZCCHC3 clones per animal revealed substantial amino acid diversity among cynomolgus macaques. We selected 12 representative variants and examined their antiviral activity against several retroviral vectors derived from HIV-1, simian immunodeficiency virus, feline immunodeficiency virus, and murine leukemia virus. Moreover, using replication-competent HIV-1, we showed that selected cynomolgus macaque ZCCHC3 variants can affect both viral production and viral infectivity. These results suggest that the genetic and functional diversity of ZCCHC3 is not limited to humans and underscore the importance of considering ZCCHC3 variation in cynomolgus macaques when using them as animal models for HIV-1-related research.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892071","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":"Staphylococcal Extracellular Complement-Binding Protein Induces IL-4 Production in Murine Basophils.","authors":"Haruka Sakakibara, Shion Kamada, Rikuto Iwata, Hina Kiriyama, Muneshige Tokugawa, Isamu Ogawa, Shigeaki Hida, Saotomo Itoh","doi":"10.1111/1348-0421.70086","DOIUrl":"https://doi.org/10.1111/1348-0421.70086","url":null,"abstract":"<p><p>Staphylococcus aureus is responsible for a wide range of pyogenic infections, food poisoning, and allergic inflammation. S. aureus produces a very wide variety of proteinaceous exotoxins, which are classified by structure as β-barrel pore-forming toxin, oligonucleotide/oligosaccharide-binding (OB)-fold/β-grasp proteins, and triple-helix bundle-containing proteins. We previously reported that three staphylococcal exotoxins belonging to the first two groups activate basophils and mast cells, which are innate immune cells that play a central role in allergic inflammation. In this study, we focused on a group of triple-helix bundle-containing toxins and examined their ability to activate murine bone marrow-derived mast cells and basophils. Extracellular complement-binding protein (Ecb), previously known as a complement inhibitor, was found to induce IL-4 and IL-6 production in basophils but not that of IL-6 and IL-13 in mast cells. Ecb did not induce IL-4 production in murine splenocytes or CD4<sup>+</sup> T cells, suggesting that it is a basophil-specific activator. Ecb-induced IL-4 expression in basophils in the absence of serum. The C3-binding-deficient mutant of Ecb also activated basophils, indicating that Ecb activates basophils independently of its complement-inhibiting activity. Dasatinib, a Src kinase inhibitor, prevented Ecb-induced IL-4 production in basophils, suggesting that the activation required a Src family kinase. These findings reveal a novel function of Ecb, that is, the activation of basophils to produce IL-4 in an IgE-independent manner, and suggest a dual Ecb contribution to immune evasion-by interfering with complement activation and skewing Th2 immunity-and a role in the development of allergic inflammation-by inducing IL-4 production.</p>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148713301","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}
Man Liu, Da Teng, Jiajia Wu, Sayumi Gouchi, Shinnosuke Fukushima, Tomoyuki Honda
{"title":"Genomic Characterization of a Novel Victorivirus Detected in a Sample Derived From a Human-Biting Tick in Japan","authors":"Man Liu, Da Teng, Jiajia Wu, Sayumi Gouchi, Shinnosuke Fukushima, Tomoyuki Honda","doi":"10.1111/1348-0421.70067","DOIUrl":"10.1111/1348-0421.70067","url":null,"abstract":"<div>\u0000 \u0000 <p>Surveillance of tick-associated viruses may contribute to our understanding of viral diversity and evolution. Here, we identified a novel victorivirus in a sample derived from a human-biting tick, <i>Amblyomma testudinarium</i>, in Japan. The viral sequence was identified by metatranscriptomic sequencing of total RNA extracted from Vero cells treated with tick homogenate. The viral sequence was 4621 bp in length and contained two major open reading frames predicted to encode a putative coat protein (CP) and a putative RNA-dependent RNA polymerase (RdRp), respectively. The two open reading frames overlapped at the tetranucleotide sequence AUGA. The C-terminal region of putative CP was enriched in alanine, glycine, and proline residues. All these features are similar to those commonly observed in victoriviruses. Phylogenetic analyses based on the amino acid sequences of the putative CP and RdRp showed that the virus belongs to the genus <i>Victorivirus</i> of the family <i>Pseudototiviridae</i>. We therefore designated this putative virus as Amblyomma testudinarium-associated victorivirus 1 (ATaVV1). These findings expand our current knowledge of hidden viral diversity in tick-associated samples.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 8","pages":"361-369"},"PeriodicalIF":1.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302410","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 of a Plasmid-Mediated Tellurite-Resistance Gene Operon Conferring High-Level Tellurite Resistance in Escherichia Albertii","authors":"Yuki Wakabayashi, Shunya Nishijima, Takahiro Yamaguchi, Kazuko Seto, Takao Kawai","doi":"10.1111/1348-0421.70069","DOIUrl":"10.1111/1348-0421.70069","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Escherichia albertii</i> is an emerging diarrheagenic pathogen that causes foodborne outbreaks. Several selective media for <i>E. albertii</i> have been developed for outbreak investigation or surveillance of a potential contamination source. Although these selective media contain potassium tellurite (PT) as a selective agent, the genetic determinants for PT resistance in <i>E. albertii</i> are unclear. Here, we analyzed the whole genomes of our 22 <i>E. albertii</i> isolates and found three that harbored the IncHI2-type plasmid encoding the tellurite resistance operon (<i>ter</i>-operon). The minimum inhibitory concentration (MIC) value of PT against <i>ter</i>-positive <i>E. albertii</i> was 640 μg/mL for all three strains, which is higher than those against other <i>E. albertii</i> isolates (5 to 40 μg/mL). The conjugation assay using three <i>ter</i>-positive <i>E. albertii</i> strains found that two of the three <i>ter</i>-positive plasmids transferred into a PT-susceptible <i>E. coli</i> recipient when tested individually, resulting in an increase in the MIC of PT to more than 640 μg/mL. The three <i>ter</i>-positive plasmids had sequence diversity, especially in the region coding antimicrobial resistance genes. The results of a plasmid database (PLSDB) search implied the circulation of <i>ter</i>-positive IncHI2 plasmids among species belonging to several genera within the order <i>Enterobacterales</i>. Phylogenetic analysis with genomes downloaded from a public database identified the <i>ter</i>-operon in 93 of 751 <i>E. albertii</i> genomes (12.4%) belonging to multiple <i>E. albertii</i> lineages. These data suggest that the plasmid-encoded <i>ter</i>-operon plays an important role in the dissemination and acquisition of high PT resistance in <i>E. albertii</i>.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 8","pages":"370-377"},"PeriodicalIF":1.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252228","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":"Pipa Qingfei Yin Ameliorates Acne Inflammation in Mice via Suppressing Neutrophil Extracellular Traps","authors":"Liangyi Wang, Xiaodan Wu, Meihui Qi, Shihua Zhang","doi":"10.1111/1348-0421.70071","DOIUrl":"10.1111/1348-0421.70071","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit driven by <i>Cutibacterium acnes</i> colonization and the ensuing inflammatory response. Neutrophil extracellular traps (NETs) play a critical role in acne inflammation. Pipa Qingfei Decoction (PPQFY), a classic Traditional Chinese Medicine formula for acne, exhibits antibacterial and anti-inflammatory effects, but whether it regulates NETs to alleviate <i>Cutibacterium</i>-induced acne remains unclear. In vitro (keratinocytes/neutrophils) and in vivo (C57BL/6 mice) acne models were established using <i>Cutibacterium acnes</i> and treated with PPQFY, DNase I, or GSK484 (NET inhibitors). Neutrophil purity and Ly6G<sup>+</sup>CD11b<sup>+</sup> cell ratio were assessed by flow cytometry. Cell viability and proliferation were evaluated using CCK-8 and EdU assays. Levels of IL-1β, TNF-α, and MPO-DNA were measured by ELISA. Protein levels of PADI4, CitH3, and MPO were determined by western blotting. Skin pathological changes were examined by H&E staining. PPQFY reversed <i>Cutibacterium acnes</i>-induced reductions in keratinocyte viability and proliferation and suppressed the elevation of IL-1β and TNF-α. PPQFY also inhibited NET release, as evidenced by decreased levels of MPO-DNA, CitH3, and PADI4. In mice, PPQFY alleviated skin inflammation, reducing keratin thickening, inflammatory infiltration, and Ly6G<sup>+</sup>CD11b<sup>+</sup>cell accumulation. These effects were comparable to those of NET inhibitors. PPQFY ameliorates <i>Cutibacterium acnes</i>-induced acne in mice by regulating NETs, providing a novel mechanistic basis for its clinical use and identifying NETs as a potential therapeutic target for acne.</p>\u0000 </section>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 8","pages":"378-387"},"PeriodicalIF":1.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345847","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":"Distinct Innate Immune Responses Following Inoculation With a Replicon mRNA COVID-19 Vaccine","authors":"Tetsuo Nakayama, Takashi Ito, Kazuhiko Katayama","doi":"10.1111/1348-0421.70068","DOIUrl":"10.1111/1348-0421.70068","url":null,"abstract":"<div>\u0000 \u0000 <p>Innate immune responses trigger the development of adaptive immune responses through the production of cytokines. In the present study, we compared the cytokine production in mice inoculated with a novel replicon mRNA COVID-19 vaccine. Biphasic and prolonged IFN-γ production was observed after the first dose, and sustained production was observed after the second dose, whereas conventional mRNA vaccines induced a peak of IFN-γ production only on Day 1 after both first and second inoculations. These findings may be associated with the self-replicating properties of the replicon mRNA vaccine following inoculation.</p>\u0000 </div>","PeriodicalId":18679,"journal":{"name":"Microbiology and Immunology","volume":"70 8","pages":"388-391"},"PeriodicalIF":1.6,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252278","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}