Latent Virus Reactivation in Ageing, Chronic Disease, or Long COVID: Mechanisms, Immunity, and Pathogenic Synergy

Ageing and chronic diseases profoundly reshape host–virus interactions and markedly increase the risk of latent viral reactivation, which plays a pivotal role in the progression of age-related pathologies. Latent viruses, including herpesviruses (e.g., CMV, EBV, HHV-6/7, HSV-1/2, VZV), polyomaviruses (JC virus, BK virus), and endogenous retroelements (HERVs), may reactivate in the context of immunosenescence, chronic inflammation, metabolic dysregulation, and epigenetic alterations, all of which are prevalent in ageing and in individuals affected by long COVID. Altered host epigenetic regulation and RNA-binding protein function may lift constraints on viral latency, enabling viral reactivation and further disrupting immune homeostasis. Additionally, perturbed cellular pathways, such as mTOR signaling, IGF1R activity, and DNA damage response, interact with these processes, compounding their effects. Unraveling these molecular relationships is essential, as viral reactivation in these vulnerable patient populations can drive tissue degeneration, autoimmune phenomena, and carcinogenesis.This Research Topic aims to define the emerging paradigm of host–virus homeostasis breakdown across ageing, chronic disease, and long COVID. We seek to uncover the molecular, cellular, and systems-level mechanisms governing viral latency and reactivation, and to understand how these processes intersect with immune remodeling, metabolic stress, and tissue-specific vulnerability. Our goal is to foster integrative research that combines systems virology, immunology, and geroscience to clarify how key molecular pathways regulate viral latency and reactivation. In parallel, we highlight translational strategies that restore host–virus balance and mitigate virus-driven disease in vulnerable populations.We invite original research articles, comprehensive reviews, and perspectives addressing how ageing-associated inflammation, immunosenescence, and metabolic dysfunction shape latent viral persistence and reactivation.- Molecular and cellular mechanisms governing latency and reactivation of persistent viruses (e.g., EBV, CMV, HHV-6/7, HSV-1/2, VZV, HERVs, JC virus, BK virus, KSHV)- Viral immune evasion strategies and their roles in sustaining chronic inflammation- Integration of metabolic stress, DNA damage responses, and signaling pathways (e.g., mTOR, IGF1R) in viral latency control- Effects of long COVID and post-viral syndromes on latent virus dynamics- Roles of RNA-binding proteins, chromatin remodeling, and epigenetic dysregulation in viral persistence- Cellular senescence, SASP, and ageing-associated pathways influencing viral reactivation- Therapeutic strategies targeting latency, including epigenetic modulation, senolytics/enomorphics, and immune-based interrventions- Multi-omics, single-cell, and systems biology approaches to dissect host–virus interactions and identify biomarkers or therapeutic targetsWe particularly encourage studies leveraging advanced multi-omics technologies, longitudinal or spatial analyses, and innovative model systems. Submissions proposing rejuvenation or host-directed strategies with clear translational potential to restore host–virus balance in at-risk populations are especially welcomed. Topic editors: Hsiang-Chi Huang, Yifei Liao Source: https://www.frontiersin.org/research-topics/79588/latent-virus-reactivation-in-ageing-chronic-disease-or-long-covid-mechanisms-immunity-and-pathogenic-synergy