{"title":"The transactivation of human endogenous retroviruses is associated with HIV-1 reservoir, lymphocyte activation and low CD4 count in virologically suppressed PLWH","authors":"Vita Petrone , Rossana Scutari , Vincenzo Malagnino , Lorenzo Piermatteo , Mirko Compagno , Romina Salpini , Martina Giudice , Marialaura Fanelli , Elisabetta Teti , Marco Iannetta , Antonella Minutolo , Maria Mercedes Santoro , Valentina Svicher , Paola Sinibaldi Vallebona , Massimo Andreoni , Emanuela Balestrieri , Loredana Sarmati , Francesca Ceccherini-Silberstein , Sandro Grelli , Claudia Matteucci","doi":"10.1016/j.micinf.2025.105478","DOIUrl":"10.1016/j.micinf.2025.105478","url":null,"abstract":"<div><div>In the context of long-term therapy in virologically suppressed people living with HIV-1 (PLWH), the identification of new biomarkers associated with immuno-virological discordance, and the risk of disease progression is needed. Herein we investigated HERVs expression in association with immuno-virological discordance parameters for the identification of novel markers for the clinical monitoring of virologically suppressed PLWH. It is known the human endogenous retroviruses (HERVs), relics of ancestral exogenous retroviral infections comprising 8 % of human genome, could be reactivated by exogenous viruses including HIV-1. The study included 31 virologically suppressed PLWH and 10 healthy donors; blood HIV-DNA levels and residual plasma viremia were quantified by droplet digital-PCR, the expression of HERVs by RT-Real time PCR, and immunophenotyping by flow cytometry. The results revealed a dynamic association of HERVs with several virological and immunological parameters such as the HIV-1 reservoir, CD4 cell count, CD4 nadir and with CD8 and CD19 lymphocyte activation. In an era of searching innovative biomarkers for people living with HIV-1, the interconnection of HERVs with the HIV-1 reservoir and lymphocyte activation opens to further investigation on HERVs role in persistent immune activation in virologically suppressed PLWH, proposing them as potential new markers for clinical monitoring.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105478"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080485","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":"A tale of a hidden family of genetic immigrants","authors":"Hervé Perron","doi":"10.1016/j.micinf.2024.105387","DOIUrl":"10.1016/j.micinf.2024.105387","url":null,"abstract":"<div><div>Though not usual for the editors of a scientific journal to ask that a story be told to its readers, this special issue is offering an opportunity to pay tribute to all those who have made it possible for a long scientific journey to open up many research avenues, to access the discoveries of what was not known and to the understanding of what was unveiled in the field of human endogenous retroviruses. In particular, and beyond a simple fortuitous association, to show their pathogenic involvement in certain diseases whose causality has been the subject of numerous and variable hypotheses.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105387"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469339","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}
Wen Liang , Miona Stubbe , Lisa Pleninger , Anna Hofferek , Hans Stubbe , Julia Mai , Salih Özer , Dmitrij Frishman , Sabrina Schreiner , Michelle Vincendeau
{"title":"HERV reactivation by adenovirus infection is associated with viral immune regulation","authors":"Wen Liang , Miona Stubbe , Lisa Pleninger , Anna Hofferek , Hans Stubbe , Julia Mai , Salih Özer , Dmitrij Frishman , Sabrina Schreiner , Michelle Vincendeau","doi":"10.1016/j.micinf.2024.105466","DOIUrl":"10.1016/j.micinf.2024.105466","url":null,"abstract":"<div><div>Human endogenous retroviruses (HERVs), which are normally silenced by methylation or mutation, can be reactivated by a variety of environmental factors, including infection with exogenous viruses. In this work, we investigated the transcriptional activity of HERVs following infection of human liver cells (HepaRG) with human adenovirus C serotype 5 (HAdV-C5). HAdV-C5 infection results in reactivation of several HERV groups as well as differentially expressed genes. Interestingly, in HAdV-C5 infection, upregulated genes that were in close chromosomal proximity to upregulated HERV loci were associated with influencing viral carcinogenesis and inflammatory signaling. We also identified an FBXO17 transcript encoding an intronic ERVK9-11 sense sequence upon HAdV-C5 infection. FBXO17 has previously been described as an important factor in the regulation of the interferon response. This suggests that specific HERV groups may have the potential to trigger gene networks and influence viral immune responses.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105466"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882441","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":"Crosstalk between human endogenous retroviruses and exogenous viruses","authors":"Edoardo Pizzioli , Antonella Minutolo , Emanuela Balestrieri , Claudia Matteucci , Gkikas Magiorkinis , Branka Horvat","doi":"10.1016/j.micinf.2024.105427","DOIUrl":"10.1016/j.micinf.2024.105427","url":null,"abstract":"<div><div>Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections of human germ-line cells, which are mostly silenced during evolution, but could be de-repressed and play a pathological role. Infection with some exogenous viruses, including herpesviruses, HIV-1 and SARS-CoV-2, was demonstrated to induce the expression of HERV RNAs and proteins.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105427"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349786","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}
Stephanie Michael, Nicholas Liotta, Tongyi Fei, Matthew L. Bendall, Douglas F. Nixon, Nicholas Dopkins
{"title":"Endogenous retroelement expression in modeled airway epithelial repair","authors":"Stephanie Michael, Nicholas Liotta, Tongyi Fei, Matthew L. Bendall, Douglas F. Nixon, Nicholas Dopkins","doi":"10.1016/j.micinf.2024.105465","DOIUrl":"10.1016/j.micinf.2024.105465","url":null,"abstract":"<div><div>Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by impairment of the CF transmembrane conductance regulator (CFTR) via gene mutation. CFTR is expressed at the cellular membrane of epithelial cells and functions as an anion pump which maintains water and salt ion homeostasis. In pulmonary airways of CF patients, pathogens such as <em>P. aeruginosa</em> and subsequent uncontrolled inflammation damage the human airway epithelial cells (HAECs) and can be life-threatening. We previously identified that inhibiting endogenous retroelement (ERE) reverse transcriptase can hamper the inflammatory response to bacterial flagella in THP-1 cells. Here, we investigate how ERE expression is sensitive to HAEC repair and toll-like receptor 5 (TLR5) activation, a primary mechanism by which inflammation impacts disease outcome. Our results demonstrate that several human endogenous retroviruses (HERVs) and long interspersed nuclear elements (LINEs) fluctuate throughout the various stages of repair and that TLR5 activation further influences ERE expression. By considering the impact of the most common CF mutation F508del/F508del on ERE expression in unwounded HAECs, we also found that two specific EREs, L1FLnI_2p23.1c and HERVH_10p12.33, were downregulated in CF-derived HAECs. Collectively, we show that ERE expression in HAECs is sensitive to certain modalities reflective of CF pathogenesis, and specific EREs may be indicative of CF disease state and pathogenesis.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105465"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142837495","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}
Nayara I Medeiros, Daniela Silva Oliveira, Karine S Ferreira, Tatjana S L Keesen, Luiz Paulo C Rocha, Giovane R Sousa, Marcos P S Damasio, Rafaelle C G Fares-Gusmao, Ana T Chaves, Fernanda F De Araújo, Walderez O Dutra, Rodrigo Correa-Oliveira, Manoel O C Rocha, Juliana A S Gomes
{"title":"FOXP3 gene polymorphisms are associated with indeterminate clinical form of Chagas disease.","authors":"Nayara I Medeiros, Daniela Silva Oliveira, Karine S Ferreira, Tatjana S L Keesen, Luiz Paulo C Rocha, Giovane R Sousa, Marcos P S Damasio, Rafaelle C G Fares-Gusmao, Ana T Chaves, Fernanda F De Araújo, Walderez O Dutra, Rodrigo Correa-Oliveira, Manoel O C Rocha, Juliana A S Gomes","doi":"10.1016/j.micinf.2025.105544","DOIUrl":"10.1016/j.micinf.2025.105544","url":null,"abstract":"<p><p>The forkhead box protein 3 (FOXP3) transcription factor is the main marker of regulatory T-cell (Treg) development and activation, a subpopulation involved in immune system regulation, self-tolerance, and protection against infections. We previously showed that Treg cells control the exacerbated immune response and morbidity in chronic Chagas disease, by modulating the cytokine environment and killing effector cells. Although FOXP3 gene polymorphisms have already been studied in several diseases, their role in Chagas disease is underreported. This study investigated FOXP3 gene polymorphism (rs3761548) in patients with Chronic Chagas disease and the association between FOXP3 polymorphisms (-3279 C/T and -3499 G/T) with clinical forms of the disease. We show that the -3499 G/T polymorphism of the heterozygous genotype (GT) is twice as prevalent in women with indeterminate clinical form (IND). Other analyses showed that the polymorphic allele (T + -3499 G/T) is high in women with IND, suggesting a protective role for this polymorphism. This pattern is associated with high frequency of FOXP3 in Treg cells in individuals with the IND form. Our results suggest that -3499 G/T polymorphism in the FOXP3 gene may play an important role in T. cruzi infection, contributing to control and the development of the IND clinical form.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105544"},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340192","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":"Cryptococcus neoformans and the EGFR Puzzle: Uncovering a Novel mechanism for blood-brain barrier crossing.","authors":"Jingyu Zhao, Wei Fang, Yangjie Gao, Zhenzong Fa, Guizhen Wang, Julin Gu","doi":"10.1016/j.micinf.2025.105540","DOIUrl":"10.1016/j.micinf.2025.105540","url":null,"abstract":"<p><p>This study aims to investigate the molecular mechanisms by which Cryptococcus neoformans (C. neoformans) crosses the blood-brain barrier (BBB), focusing specifically on the role of the epidermal growth factor receptor (EGFR) and its ligand, HB-EGF. Cryptococcal meningitis, caused by C. neoformans, has a high mortality rate and poses a significant threat to global public health. Research indicates that C. neoformans employs various strategies to cross the BBB, with transcellular transport being particularly critical. We observed that C. neoformans infection significantly upregulates the expression and phosphorylation of EGFR in brain microvascular endothelial cells (BMECs). Silencing EGFR using siRNA technology resulted in a marked decrease in the ability of C. neoformans to traverse the BMEC monolayer. Furthermore, C. neoformans infection also upregulates EGFR ligands, such as HB-EGF, in BMECs, thereby activating the EGFR signaling pathway. This activation involves the engagement of ADAM family metalloproteinases and the metalloprotease Mpr1 from C. neoformans. The findings of this study underscore the critical role of the host EGFR signaling pathway in the ability of C. neoformans to cross the BBB and highlight potential targets for developing new therapies for infectious meningitis.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105540"},"PeriodicalIF":2.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248714","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}
Marta Gliźniewicz, Barbara Dołęgowska, Adrian Augustyniak, Rafał Rakoczy, Tomasz Kędzierski, Ewa Mijowska, Bartłomiej Grygorcewicz
{"title":"Effects of sequential administration of phage cocktail, ciprofloxacin, and caspofungin on Staphylococcus aureus and Candida albicans dual-species biofilms.","authors":"Marta Gliźniewicz, Barbara Dołęgowska, Adrian Augustyniak, Rafał Rakoczy, Tomasz Kędzierski, Ewa Mijowska, Bartłomiej Grygorcewicz","doi":"10.1016/j.micinf.2025.105531","DOIUrl":"10.1016/j.micinf.2025.105531","url":null,"abstract":"<p><p>Polymicrobial biofilms, including inter-kingdom ones, represent another threat in the post-antibiotic era. Therefore, many alternative solutions are being investigated, including phage-antibiotic synergy (PAS), which may be more effective due to the differing mechanisms of action of drugs and phages. In this study, we evaluated how different sequences of administering a bacteriophage cocktail, ciprofloxacin, and caspofungin affect the eradication of S. aureus and C. albicans in vitro (planktonic culture and in biofilms). In liquid culture, the phage → caspofungin → ciprofloxacin treatment completely eradicated both organisms. In biofilms, the most effective regimens were either the simultaneous application of all three agents or phages + ciprofloxacin followed by caspofungin. Therefore, the sequence of administration of drugs and phages is a key factor in achieving effective therapy and revealing the most synergistic combinations.</p>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":" ","pages":"105531"},"PeriodicalIF":2.6,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199603","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}