Human Endogenous Retroviruses: Epigenetic and Immune Modulators in Health and Disease

Dear Colleagues,

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that have become integrated into the human genome, constituting approximately 8% of human DNA. Although historically considered inert, increasing evidence indicates that HERVs are transcriptionally active under specific physiological and pathological conditions, with broad implications for human health and disease.

HERVs influence their host’s biology through several mechanisms. Their RNA and protein products may serve as immunostimulatory ligands, engaging pattern recognition receptors and driving proinflammatory signaling cascades. Simultaneously, HERV integration within or near regulatory elements can reshape the epigenetic landscape and alter the transcriptional activity of neighboring genes, particularly those involved in immune regulation, inflammation, and cellular stress responses. These dual roles—both as modulators of host gene expression and as active participants in innate and adaptive immune responses—position HERVs as key contributors to disease processes such as cancer, autoimmunity, and neurodegeneration.

This Special Issue seeks to present interdisciplinary research that advances our understanding of the biology, regulatory mechanisms, and disease associations of HERVs. We invite authors to submit original research articles, reviews, and computational studies addressing the following:

• The epigenetic and transcriptional regulation of HERVs;
• The immunological consequences of HERV expression;
• The roles of HERVs in exogenous virus coinfections, cancer, autoimmunity, and neurodegenerative diseases;
• The diagnostic and therapeutic relevance of HERVs.

Dr. Seyedesomaye Jasemi
Prof. Dr. Leonardo A. Sechi
Guest Editors

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