Microbes and InfectionPub Date : 2025-07-01Epub Date: 2025-06-05DOI: 10.1016/j.micinf.2025.105530
Patrick Küry , Patrice N. Marche
{"title":"Human endogenous retroviruses: The iceberg view","authors":"Patrick Küry , Patrice N. Marche","doi":"10.1016/j.micinf.2025.105530","DOIUrl":"10.1016/j.micinf.2025.105530","url":null,"abstract":"","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105530"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248715","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}
Microbes and InfectionPub Date : 2025-07-01Epub Date: 2025-02-04DOI: 10.1016/j.micinf.2025.105479
Urs Meyer , Iris Katharina Penner
{"title":"Endogenous retroviruses in neurodevelopmental, psychotic and cognitive disorders","authors":"Urs Meyer , Iris Katharina Penner","doi":"10.1016/j.micinf.2025.105479","DOIUrl":"10.1016/j.micinf.2025.105479","url":null,"abstract":"<div><div>Endogenous retroviruses (ERVs) are inherited retroviral genomic elements that integrated into the mammalian genome through germline infections and insertions during evolution. Human ERVs (HERVs) comprise approximately 8 % of the human genome and are increasingly recognized to be involved in the etiology and pathophysiology of numerous brain disorders. In this narrative review, we summarize the existing evidence linking abnormal HERV expression to neurodevelopmental and psychosis-related disorders and discuss how these retroviral elements may contribute to the heterogeneity in clinical outcomes. We also review the findings suggesting that aberrant HERV expression contribute to late-onset cognitive disorders with neurodegenerative components, such as Alzheimer's disease (AD) and other forms of dementia. The evidence implicating abnormal HERV expression in neurodevelopmental, psychotic, and cognitive disorders is manifold and stems from diverse research fields, including human post-mortem brain studies, serological investigations, gene expression analyses, and clinical trials with HERV-specific pharmacological compounds. The recent establishment and use of animal models offer a complementary experimental platform that will help establish causal relationships and identify specific disease pathways affected by abnormal HERV expression. Yet, significant gaps persist in understanding the role of HERVs in neurodevelopmental, psychotic, and cognitive disorders, particularly concerning the specificity and stability of abnormal HERV expression in these conditions. Addressing these questions appears crucial for optimizing the potential benefits of therapeutic interventions aimed at targeting abnormal HERV expression across the broad spectrum of HERV-associated disorders of the central nervous system.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105479"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365055","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":"HERV-W ENV transcription in B cells predicting symptomatic COVID-19 and risk for long COVID can express a full-length protein despite stop codon in mRNA from chromosome X via a ribosome readthrough","authors":"Joanna Brunel , Julien Paganini , Melissa Galloux , Benjamin Charvet , Hervé Perron","doi":"10.1016/j.micinf.2024.105431","DOIUrl":"10.1016/j.micinf.2024.105431","url":null,"abstract":"<div><div>The human genome comprises 8 % of endogenous retroviruses (HERVs). Though HERVS contribute to physiological functions, copies retained pathogenic potential. The HERV-W ENV protein was shown expressed in patients with worse COVID-19 symptoms and post-COVID syndrome. A significant detection of the mRNA encoding HERV-W ENV from patients with COVID-19 in B cells from RNAseq reads obtained from peripheral blond mononuclear cells. This data stratified with increased COVID-19 symptoms or with post-acute sequelae of COVID-19 (long COVID) after 3 months. The HERV-W <em>ENV-U3R</em> RNA was confirmed to display the best alignment with chromosome X ERVWE2 locus. However, a stop codon precluding its translation was re-addressed after recent understandings of ribosome readthrough mechanisms. Experimental results evidenced that this HERV gene can effectively express a full-length protein in the presence of molecules allowing translation via a readthrough mechanism at the ribosome level. Results not only confirm HERV-W <em>ENV</em> RNA origin in these patients but show for the first time how a defective HERV copy can be translated into a complete protein when specific factors make it possible at the ribosome level. The present proof of concept now requires further studies to identify the factors involved in this newly understood mechanism, following SARS-CoV-2 exposure.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105431"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142469725","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}
Microbes and InfectionPub Date : 2025-05-01Epub Date: 2025-03-11DOI: 10.1016/j.micinf.2025.105483
BiXia Liu , YaRu Gu , YangXue Ou , LuXuan Liu , WenHao Wang , JinRui Zhou , Ying Wang , YeXiang Du , Jing Xie , Yuan Liu , Rui Zhang , QianFei Zuo , Bin Wang
{"title":"Protection conferred by mucosal novel bivalent Klebsiella pneumoniae vaccine immunization associates with presence of lung CD4+ TRM","authors":"BiXia Liu , YaRu Gu , YangXue Ou , LuXuan Liu , WenHao Wang , JinRui Zhou , Ying Wang , YeXiang Du , Jing Xie , Yuan Liu , Rui Zhang , QianFei Zuo , Bin Wang","doi":"10.1016/j.micinf.2025.105483","DOIUrl":"10.1016/j.micinf.2025.105483","url":null,"abstract":"<div><div><em>Klebsiella pneumoniae</em> is the principal cause of hospital-acquired infection with a high morbidity and mortality in immunocompromised individuals, yet no vaccine is approved. Here, we developed a novel bivalent subunit vaccine for the prevention of <em>K. pneumoniae</em> infection based on the outer membrane protein GlnH and the fimbriae protein FimA. The survival rate of immunized mice was significantly increased compared to that of unimmunized mice, while the bacterial burden, weight loss, and lung pathology were drastically reduced. Furthermore, vaccine-elicited CD4<sup>+</sup> T<sub>RM</sub> cells were observed in lung tissues and appeared to play a critical role in vaccine efficacy. Transcriptomic analysis of total lung tissues from mice treated by FTY720 (S1PR1 inhibitor that blocks lymphocyte egress from secondary lymphoid structures) showed that cell activation, cytokine secretion and enhancement of the killing ability of neutrophils were related to the mechanism of protection against <em>K. pneumoniae</em> infection. These findings indicate that GlnH and FimA are effective candidate bivalent vaccine to fight <em>K. pneumoniae</em> infection.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105483"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625409","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}
Microbes and InfectionPub Date : 2025-05-01Epub Date: 2025-04-17DOI: 10.1016/j.micinf.2025.105504
Jing Chen , Yaoling Wang , Xinyi Chen , Fangfang Di, Guanghua Wang, Runjie Zhang, Jin Qiu
{"title":"Metabolic profile and disordered glycerophospholipid metabolism in recurrent vulvovaginal candidiasis","authors":"Jing Chen , Yaoling Wang , Xinyi Chen , Fangfang Di, Guanghua Wang, Runjie Zhang, Jin Qiu","doi":"10.1016/j.micinf.2025.105504","DOIUrl":"10.1016/j.micinf.2025.105504","url":null,"abstract":"<div><div>Recurrent vulvovaginal candidiasis (RVVC) takes a toll not only on women's reproductive system but also on patients' life quality. The pathogenesis is still not fully understood. This study sought to explore metabolic profile of vaginal discharge from RVVC patients using non-targeted metabolomics and investigate potential bioactive functions of metabolites. The metabolic spectrum of RVVC patients was remarkably distinguished from healthy control and VVC patients. 324 metabolites with significant difference were detected in RVVC compared with control group, of which 239 were upregulated and 85 were downregulated. Moreover, compared with VVC, RVVC had a total of 67 significantly different metabolites including 43 upregulated metabolites and 24 downregulated metabolites. KEGG pathway analysis showed that Glycerophospholipid (GPL) metabolic pathway and PPAR signaling pathway were significantly changed in RVVC and the metabolites enriched into GPL metabolic pathway including LysoPC(18:1(11Z)), LysoPC(20:3(5Z,8Z,11Z)), PC(16:0/20:2(11Z,14Z)), PC(18:1(11Z)/18:1(9Z)) and PE(22:2(13Z,16Z)/18:3(9Z,12Z,15Z)) were significantly changed in RVVC patients and of high AUC values. In addition, the highest increased LysoPS(18:1(9Z)/0:0) in RVVC was demonstrated to not only inhibit the proliferation and migration of vaginal epithelial cells but also promote apoptosis. Molecular docking which showed strongly bind between LysoPS(18:1(9Z)/0:0) and PPAR-γ lead to a hypothesis that LysoPS(18:1(9Z)/0:0) may have an influence on RVVC through PPAR signaling pathway. Our findings provide new perspectives in understanding the pathogenesis of RVVC.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105504"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144031505","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":"Porcine alveolar macrophages and nasal epithelial cells internalize porcine epidemic diarrhea virus (PEDV) but do not support its replication in vitro","authors":"Carlos López-Figueroa , Noelia Carmona-Vicente , Esmeralda Cano , Núria Navarro , Cristina Risco , Joan Repullés , Joaquim Segalés , Júlia Vergara-Alert","doi":"10.1016/j.micinf.2025.105500","DOIUrl":"10.1016/j.micinf.2025.105500","url":null,"abstract":"<div><div>Porcine epidemic diarrhea virus (PEDV) primarily targets enterocytes subsequent to fecal-oral exposure, resulting in severe gastrointestinal disease in neonatal piglets. However, recent evidence suggests potential alternative PEDV entry and replication routes via the respiratory tract. The present study delved into the possibility of an alternative pathway for PEDV infection in porcine alveolar macrophages (PAMs), 3D4/21 cells (3D4), and nasal turbinate epithelial cells, focusing on the inherent innate antiviral and anti-inflammatory immune responses to a cell-adapted non-S INDEL USA PEDV strain. CCL-81 cells were used as positive controls of infection, while non-infected CCL-81, PAMs, and 3D4 cells served as negative controls. Quantification of the viral load in cells and supernatants (SN) was carried out at multiple hours post-inoculation (hpi; 0, 6, 12, 24, 48, 72, and 96 hpi) using RT-qPCR, while infectious virus titers were assessed through TCID<sub>50</sub>/ml on cell cultures and immunofluorescence (IF) staining. PEDV capture and internalization were examined using IF at 24 and 48 hpi, alongside the evaluation of the presence of viral particles and ultrastructural changes using transmission electron microscopy (TEM). Proinflammatory and antiviral cytokine levels in SN were measured using ELISA and Luminex. In both PAMs and 3D4 cells, PEDV RNA levels peaked at 12 hpi in cells and SN, then declined gradually without significant differences between cell types. Only few PAMs and 3D4 cells tested positive for PEDV IF, with no increase in positive cells between 24 and 48 hpi. TEM did not reveal viral particles or changes in cell organelles, and no proinflammatory or antiviral cytokine expression was detected in either cell type of macrophage cells. In parallel, nasal turbinate organoids (NTOs), cultivated as 2D monolayer and at an air-liquid interface (ALI), were exposed to PEDV, with RT-qPCR and IF conducted at 24 hpi. Despite the cultivation technique used, similar levels of PEDV RNA were detected in both the cells and the SN, with positive results observed for PEDV IF. Overall, while PAMs, 3D4 cells and nasal epithelium can capture and internalize PEDV, they do not support viral replication or trigger an antiviral or anti-inflammatory responses.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105500"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780473","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":"Immunostimulatory effects of Hsp70 fragments-modified DCs: A computational and experimental study in HIV vaccine design","authors":"Elahe Akbari , Alireza Milani , Parisa Moradi Pordanjani , Masoud Seyedinkhorasani , Elnaz Agi , Azam Bolhassani","doi":"10.1016/j.micinf.2025.105480","DOIUrl":"10.1016/j.micinf.2025.105480","url":null,"abstract":"<div><h3>Background</h3><div>Dendritic cells (DCs) loaded with HIV-1 antigens have been explored as a promising therapeutic approach to overcome HIV-1 infection. Heat shock proteins (Hsps) can improve cross-presentation of linked antigens by DCs. Our aim was a comprehensive <em>in silico</em>, <em>in vitro</em>, and <em>in vivo</em> evaluation of fusion proteins comprising the <em>N</em>- and C-terminal regions of Hsp70 (<em>i.e.,</em> NT-Hsp70 and CT-Hsp70) as an adjuvant linked to HIV-1 Nef antigen in development of DCs-based vaccine candidates.</div></div><div><h3>Methods</h3><div>Computational analyses of the NT-Hsp70-Nef and CT-Hsp70-Nef fusion constructs were performed, and their structural features and docking ability with toll-like or endocytic receptors were evaluated. The effectiveness of DCs loaded with the fusion proteins in eliciting immunity was assessed in mice. Cytokine secretion levels from splenocytes exposed to single-cycle replicable (SCR) HIV-1 were also measured <em>in vitro</em>.</div></div><div><h3>Results</h3><div>The DCs pulsed with the fusion constructs induced robust cellular and humoral immune responses in mice and infected splenocytes. The CT-Hsp70 region showed better docking scores with immune receptors and superior adjuvanticity for inducing Nef-specific immune responses (Th1 and CTL activity) compared to the NT-Hsp70 region in DC-based immunization.</div></div><div><h3>Conclusions</h3><div>The CT-Hsp70-Nef protein demonstrated promising results in both computational and experimental analyses compared to the NT-Hsp70-Nef protein.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105480"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432538","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":"Host–parasite interactions after in vitro infection of human macrophages by Leishmania major: Dual analysis of microRNA and mRNA profiles reveals regulation of key processes through time kinetics","authors":"Chiraz Atri , Ghada Mkannez , Hanène Attia , Rabiaa Manel Sghaier , Aymen Bali , Ali Ben-Cheikh , Imen Rabhi , Béatrice Regnault , David Piquemal , Kais Ghedira , Koussay Dellagi , Dhafer Laouini , Fatma Zahra Guerfali","doi":"10.1016/j.micinf.2025.105502","DOIUrl":"10.1016/j.micinf.2025.105502","url":null,"abstract":"<div><div>Micro-RNAs are a class of small non-coding ribonucleic acids that concomitantly regulate the expression of tens to hundreds of genes. To reduce the host's defense, <em>Leishmania</em> parasites hijack the cellular functions of their macrophage's targets through gene expression regulation. Only few studies have attempted to correlate miRNAs and mRNAs expressions within the same samples in the context of cellular parasitism.</div><div>In this study, the profiling of human macrophages, <em>in vitro</em> infected by <em>L. major</em> parasites, was performed at both the mRNA transcriptomic level and the expression of a set of 365 miRNAs, and we correlated their expressions in search for a common molecular signature.</div><div>Both mRNA and miRNA profiles were monitored during the first 24 h post-infection to capture potential time-dependent fluctuations. We then cross-correlated the cellular biological processes and the pathways associated to the predicted targets of miRNAs and to the differentially expressed mRNAs at all time points of infection on the same samples.</div><div>Besides revealing the classical activation of immune signaling pathways, the mRNA-micro-RNAs correlation study highlighted other common regulatory inflammatory biological processes, allowing identification of rapidly modulated pathways, and bringing further evidence on the early molecular cross talk that take place between <em>Leishmania</em> and infected cells.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105502"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018212","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}
Microbes and InfectionPub Date : 2025-05-01Epub Date: 2025-05-16DOI: 10.1016/j.micinf.2025.105529
Changzhou Feng , Haining Li , Ying Zhou, Chu Zhang, Jin Yang, Haiqing Wang
{"title":"No association between anti-cytomegalovirus seropositivity and arthritis: evidence from the cross-sectional epidemiology and genetic association analyses","authors":"Changzhou Feng , Haining Li , Ying Zhou, Chu Zhang, Jin Yang, Haiqing Wang","doi":"10.1016/j.micinf.2025.105529","DOIUrl":"10.1016/j.micinf.2025.105529","url":null,"abstract":"<div><div>Human cytomegalovirus (CMV), a β-herpesvirus associated with chronic inflammation and lifelong latency, has been implicated in the pathogenesis of arthritis. However, the nature of this relationship remains controversial. In this study, we integrate cross-sectional epidemiology analyses, genetic correlation assessments, and Mendelian randomization (MR) approaches to elucidate the potential association between CMV infection and arthritis-related conditions. Observational analysis of 5133 participants from the NHANES database revealed a positive association between CMV IgG seropositivity and arthritis (OR: 1.24; 95 % CI: 1.03–1.48; <em>P</em> = 0.02), particularly with the rheumatoid arthritis (RA) subtype (OR: 1.94; 95 % CI: 1.21–3.12; <em>P</em> < 0.01). However, these associations lost statistical significance after adjustment for multiple covariates (all <em>P</em> > 0.05). Subgroup and interaction analyses across different demographic and clinical subpopulations further confirmed the absence of these associations. Similarly, subtype analyses indicated no significant association between CMV IgG seropositivity and osteoarthritis (OA), other-arthritis, or unknown-arthritis, even before covariate adjustment. Linkage disequilibrium score regression (LDSC) analysis did not reveal a significant genetic correlation between anti-CMV IgG levels and arthritis, including RA and OA (all <em>P</em> > 0.05), suggesting no shared genetic basis. Furthermore, bidirectional MR analyses found no evidence of a causal relationship between CMV antibody responses—including IgG and three CMV-related peptide antigens (pp28, pp52, and pp150)—and arthritis, RA, or OA (all <em>P</em> > 0.05). Collectively, these findings suggest that previously reported positive associations between CMV seropositivity and arthritis may have been confounded by other covariates rather than reflecting a true causal relationship.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 4","pages":"Article 105529"},"PeriodicalIF":2.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094181","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}