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Endogenous retroviruses (ERVs) are remnants of retroviral infections that have become stably integrated into host germline genomes. Far beyond passive genomic elements, ERVs actively shape host evolution through complex mechanisms involving genetic innovation, immune modulation, and species adaptation. This review provides a comprehensive synthesis of ERV biology, highlighting recent advances in their classification, amplification mechanisms, and epigenetic silencing. Particular emphasis is placed on the cross-talk between ERVs and exogenous retroviruses (XRVs), demonstrating how receptor competition, recombination, and immune evasion contribute to virus-host co-evolution. We explore ERVs as molecular markers for phylogenetic reconstruction, with case studies such as Koala retrovirus (KoRV) and HERV-K illustrating regional transmission dynamics and co-opted immune functions. Additionally, we discuss the functional domestication of ERVs into regulatory elements, non-coding RNAs, and envelope-derived fusion proteins that influence gene expression, antiviral defense, and placental development.
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http://dx.doi.org/10.3390/genes16080964 | DOI Listing |
Genes (Basel)
August 2025
Division of Computational Biology, Mayo Clinic, Rochester, MN 55905, USA.
Background/objectives: Human endogenous retroviruses (ERVs) are genomic sequences integrated into the human genome from ancestral exogenous retroviruses and are epigenetically silenced under normal conditions. Growing evidence has shown that they can be reactivated in human diseases such as cancers and autoimmune diseases. However, their clinical implications in colon cancer are yet to be explored.
View Article and Find Full Text PDFGenes (Basel)
August 2025
Key Laboratory of Cell and Molecular Intelligent Design and Development of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Endogenous retroviruses (ERVs) are remnants of retroviral infections that have become stably integrated into host germline genomes. Far beyond passive genomic elements, ERVs actively shape host evolution through complex mechanisms involving genetic innovation, immune modulation, and species adaptation. This review provides a comprehensive synthesis of ERV biology, highlighting recent advances in their classification, amplification mechanisms, and epigenetic silencing.
View Article and Find Full Text PDFSci Adv
August 2025
Center for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
Human endogenous retroviruses (HERVs) are remnants of ancient infections that comprise ~8% of the human genome. The HERV-K envelope glycoprotein (Env) is aberrantly expressed in cancers, autoimmune disorders, and neurodegenerative diseases, and is targeted by patients' own antibodies. However, a lack of structural information has limited molecular and immunological studies of the roles of HERVs in disease.
View Article and Find Full Text PDFWorld J Methodol
September 2025
Department of Surgery, Ascension St Agnes Hospital, Baltimore, MD 21009, United States.
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic condition marked by recurring gastrointestinal inflammation. While immune, genetic, and environmental factors are well-studied, the gut virome has received less attention. This editorial highlights the work which investigates the gut virome's role in IBD and its interactions with the bacterial microbiome and host immune system.
View Article and Find Full Text PDFBiomol Biomed
August 2025
Department of Biomedical Sciences, College of Osteopathic Medicine, Liberty University, Lynchburg, VA, USA.
Decitabine (DAC), a DNA methyltransferase inhibitor (DNMTi), is clinically effective in hematological malignancies such as myelodysplastic syndrome and acute myeloid leukemia, but its precise antineoplastic mechanisms remain incompletely understood. Beyond promoter demethylation, DAC is known to activate endogenous retroviruses (ERVs) and trigger type I interferon (IFN-I) responses, a phenomenon known as viral mimicry. The aim of this study was to investigate the roles of the mouse mammary tumor virus (MMTV) and interferon-β (IFN-β) in DAC-mediated tumor suppression.
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