Pub Date : 2025-09-01DOI: 10.1016/j.micinf.2025.105557
Kuangyi Charles Wei , Srinithi Purushothaman , Francesca Azzato , Kate S. Baker , Kira Waagner Birkeland , Sofia Brunet , Josefina Campos , Thomas R. Connor , Christian G. Giske , Gilbert Greub , Erika Tång Hallbäck , Dag Harmsen , Emma B. Hodcroft , Matthew T.G. Holden , Jobin Jacob , Andre Kahles , Amaya Campillay Lagos , Samuel Lipworth , Elin Loo , Paolo Miotto , Adrian Egli
{"title":"Conference report: The second Bacterial Genome Sequencing Pan-European Network conference","authors":"Kuangyi Charles Wei , Srinithi Purushothaman , Francesca Azzato , Kate S. Baker , Kira Waagner Birkeland , Sofia Brunet , Josefina Campos , Thomas R. Connor , Christian G. Giske , Gilbert Greub , Erika Tång Hallbäck , Dag Harmsen , Emma B. Hodcroft , Matthew T.G. Holden , Jobin Jacob , Andre Kahles , Amaya Campillay Lagos , Samuel Lipworth , Elin Loo , Paolo Miotto , Adrian Egli","doi":"10.1016/j.micinf.2025.105557","DOIUrl":"10.1016/j.micinf.2025.105557","url":null,"abstract":"","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 7","pages":"Article 105557"},"PeriodicalIF":2.7,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144817105","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}
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.
在病毒学抑制的HIV-1感染者（PLWH）长期治疗的背景下，需要鉴定与免疫-病毒学不一致和疾病进展风险相关的新生物标志物。在此，我们研究了herv表达与免疫病毒学不一致参数的关系，以鉴定用于临床监测病毒学抑制PLWH的新标记。众所周知，人类内源性逆转录病毒（herv）是祖先外源性逆转录病毒感染的遗迹，占人类基因组的8%，可以被包括HIV-1在内的外源性病毒重新激活。该研究包括31名病毒学抑制的PLWH和10名健康供体；采用液滴数字PCR法检测小鼠血液HIV-DNA水平和残留血浆病毒血症，RT-Real - time PCR法检测小鼠herv表达，流式细胞术检测小鼠免疫表型。结果显示，herv与若干病毒学和免疫学参数（如HIV-1库、CD4细胞计数、CD4最低点以及CD8+和CD19淋巴细胞活化）存在动态关联。在为HIV-1感染者寻找创新生物标志物的时代，herv与HIV-1储存库和淋巴细胞激活的相互联系为进一步研究herv在病毒学抑制的PLWH中持续免疫激活中的作用开辟了空间，并提出了它们作为临床监测的潜在新标志物。
{"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}
Pub Date : 2025-07-01DOI: 10.1016/j.micinf.2024.105387
Hervé Perron
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.
{"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}
Pub Date : 2025-07-01DOI: 10.1016/j.micinf.2024.105466
Wen Liang , Miona Stubbe , Lisa Pleninger , Anna Hofferek , Hans Stubbe , Julia Mai , Salih Özer , Dmitrij Frishman , Sabrina Schreiner , Michelle Vincendeau
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.
{"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}
Pub Date : 2025-07-01DOI: 10.1016/j.micinf.2024.105382
Joel Gruchot , Laura Reiche , Luisa Werner , Felisa Herrero , Jessica Schira-Heinen , Urs Meyer , Patrick Küry
The endogenous retrovirus type W (HERV-W) is a human-specific entity, which was initially discovered in multiple sclerosis (MS) patient derived cells. We initially found that the HERV-W envelope (ENV) protein negatively affects oligodendrogenesis and controls microglial cell polarization towards a myelinated axon associated and damaging phenotype. Such first functional assessments were conducted ex vivo, given the human-specific origin of HERV-W. Recent experimental evidence gathered on a novel transgenic mouse model, mimicking activation and expression of the HERV-W ENV protein, revealed that all glial cell types are impacted and that cellular fates, differentiation, and functions were changed. In order to identify HERV-W-specific signatures in glial cells, the current study analyzed the transcriptome of ENV protein stimulated microglial- and astroglial cells and compared the transcriptomic signatures to lipopolysaccharide (LPS) stimulated cells, owing to the fact that both ligands can activate toll-like receptor-4 (TLR-4). Additionally, a comparison between published disease associated glial signatures and the transcriptome of HERV-W ENV stimulated glial cells was conducted. We, therefore, provide here for the first time a detailed molecular description of specific HERV-W ENV evoked effects on those glial cell populations that are involved in smoldering neuroinflammatory processes relevant for progression of neurodegenerative diseases.
{"title":"Molecular dissection of HERV-W dependent microglial- and astroglial cell polarization","authors":"Joel Gruchot , Laura Reiche , Luisa Werner , Felisa Herrero , Jessica Schira-Heinen , Urs Meyer , Patrick Küry","doi":"10.1016/j.micinf.2024.105382","DOIUrl":"10.1016/j.micinf.2024.105382","url":null,"abstract":"<div><div>The endogenous retrovirus type W (HERV-W) is a human-specific entity, which was initially discovered in multiple sclerosis (MS) patient derived cells. We initially found that the HERV-W envelope (ENV) protein negatively affects oligodendrogenesis and controls microglial cell polarization towards a myelinated axon associated and damaging phenotype. Such first functional assessments were conducted <em>ex vivo</em>, given the human-specific origin of HERV-W. Recent experimental evidence gathered on a novel transgenic mouse model, mimicking activation and expression of the HERV-W ENV protein, revealed that all glial cell types are impacted and that cellular fates, differentiation, and functions were changed. In order to identify HERV-W-specific signatures in glial cells, the current study analyzed the transcriptome of ENV protein stimulated microglial- and astroglial cells and compared the transcriptomic signatures to lipopolysaccharide (LPS) stimulated cells, owing to the fact that both ligands can activate toll-like receptor-4 (TLR-4). Additionally, a comparison between published disease associated glial signatures and the transcriptome of HERV-W ENV stimulated glial cells was conducted. We, therefore, provide here for the first time a detailed molecular description of specific HERV-W ENV evoked effects on those glial cell populations that are involved in smoldering neuroinflammatory processes relevant for progression of neurodegenerative diseases.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105382"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469340","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}
Pub Date : 2025-07-01DOI: 10.1016/j.micinf.2024.105460
Laura Reiche , Benedikt Plaack , Maike Lehmkuhl , Vivien Weyers , Joel Gruchot , Daniel Picard , Hervé Perron , Marc Remke , Christiane Knobbe-Thomsen , Guido Reifenberger , Patrick Küry , David Kremer
Gliomas are the most common parenchymal tumors of the central nervous system (CNS). With regard to their still unclear etiology, several recent studies have provided evidence of a new category of pathogenic elements called human endogenous retroviruses (HERVs) which seem to contribute to the evolution and progression of many neurological diseases such as amyotrophic lateral sclerosis (ALS), schizophrenia, chronic inflammatory polyneuropathy (CIDP) and, particularly, multiple sclerosis (MS). In these diseases, HERVs exert effects on cellular processes such as inflammation, proliferation, and migration. In previous studies, we demonstrated that in MS, the human endogenous retrovirus type-W envelope protein (HERV-W ENV) interferes with lesion repair through the activation of microglia (MG), the innate myeloid immune cells of the CNS. Here, we now show that HERV-W ENV is also present in the microglial cells (MG) of the tumor microenvironment (TME) in gliomas. It modulates the behavior of glioblastoma (GBM) cell lines in GBM/MG cocultures by altering their gene expression, secreted cytokines, morphology, proliferation, and migration properties and could thereby contribute to key tumor properties.
胶质瘤是中枢神经系统（CNS）最常见的实质性肿瘤。关于神经胶质瘤尚不明确的病因，最近的一些研究提供了证据，证明有一类新的致病因子被称为人类内源性逆转录病毒（HERVs），它们似乎是许多神经系统疾病（如肌萎缩性脊髓侧索硬化症（ALS）、精神分裂症、慢性炎症性多发性神经病（CIDP），尤其是多发性硬化症（MS））演变和发展的诱因。在这些疾病中，HERVs 对炎症、增殖和迁移等细胞过程产生影响。在之前的研究中，我们证实在多发性硬化症中，人类内源性逆转录病毒 W 型包膜蛋白（HERV-W ENV）通过激活中枢神经系统的先天性髓系免疫细胞小胶质细胞（MG）干扰病变修复。现在，我们发现 HERV-W ENV 也存在于胶质瘤中肿瘤微环境（TME）的小胶质细胞（MG）中。它通过改变胶质母细胞瘤（GBM）细胞系的基因表达、分泌细胞因子、形态、增殖和迁移特性，调节胶质母细胞瘤（GBM）细胞系在GBM/MG共培养物中的行为，并可能因此导致关键的肿瘤特性。
{"title":"HERV-W envelope protein is present in microglial cells of the human glioma tumor microenvironment and differentially modulates neoplastic cell behavior","authors":"Laura Reiche , Benedikt Plaack , Maike Lehmkuhl , Vivien Weyers , Joel Gruchot , Daniel Picard , Hervé Perron , Marc Remke , Christiane Knobbe-Thomsen , Guido Reifenberger , Patrick Küry , David Kremer","doi":"10.1016/j.micinf.2024.105460","DOIUrl":"10.1016/j.micinf.2024.105460","url":null,"abstract":"<div><div>Gliomas are the most common parenchymal tumors of the central nervous system (CNS). With regard to their still unclear etiology, several recent studies have provided evidence of a new category of pathogenic elements called human endogenous retroviruses (HERVs) which seem to contribute to the evolution and progression of many neurological diseases such as amyotrophic lateral sclerosis (ALS), schizophrenia, chronic inflammatory polyneuropathy (CIDP) and, particularly, multiple sclerosis (MS). In these diseases, HERVs exert effects on cellular processes such as inflammation, proliferation, and migration. In previous studies, we demonstrated that in MS, the human endogenous retrovirus type-W envelope protein (HERV-W ENV) interferes with lesion repair through the activation of microglia (MG), the innate myeloid immune cells of the CNS. Here, we now show that HERV-W ENV is also present in the microglial cells (MG) of the tumor microenvironment (TME) in gliomas. It modulates the behavior of glioblastoma (GBM) cell lines in GBM/MG cocultures by altering their gene expression, secreted cytokines, morphology, proliferation, and migration properties and could thereby contribute to key tumor properties.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 5","pages":"Article 105460"},"PeriodicalIF":2.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692929","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}
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.
{"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}
Pub Date : 2025-07-01DOI: 10.1016/j.micinf.2024.105465
Stephanie Michael, Nicholas Liotta, Tongyi Fei, Matthew L. Bendall, Douglas F. Nixon, Nicholas Dopkins
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 P. aeruginosa 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.
{"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}
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