Persistent immune remodeling after chronic viral infection

Chronic viral infections raise an important cross-pathogen question: to what extent do different viruses converge on shared mechanisms that drive long-lasting, dysfunctional immune memory, persisting even after viral suppression or clearance? A particularly important, yet underexplored, aspect is how these processes unfold within tissue-resident and mucosal compartments. Tissue-resident memory T cells (TRM), along with the metabolic and epigenetic programs that support them, are increasingly recognized as key contributors to the persistence of altered immune states. Across organs such as the liver, gastrointestinal tract, and lymphoid tissues, prior or ongoing viral exposure can leave durable imprints on both local and systemic immunity. Observations across different viral infections point to a mix of shared patterns and virus-specific effects. Cytomegalovirus is a well-established driver of age-associated immune remodeling and immunosenescence, though its impact varies by host context. Hepatitis B and Hepatitis C infection reshape memory T cell and B cell populations in ways that do not always resolve after viral control — in HBV, functional cure is not only defined by loss of detectable viral markers, but also by the extent to which antiviral immunity is restored and durable. Successful HCV clearance does not always lead to full reversal of immune dysfunction, indicating that epigenetic and metabolic reprogramming of immune cells may outlast the infection itself. HIV offers an important point of comparison: even with effective viral suppression, many individuals retain persistent T cell exhaustion and impaired memory reconstitution, pointing to tissue-level dysfunction that goes beyond circulating immune markers. Findings from SARS-CoV-2 and Epstein-Barr virus further broaden this perspective, highlighting the diversity of ways in which viral exposure can perturb immune memory — from post-acute immune dysregulation to latency-driven remodeling of memory B and T cell compartments. This Research Topic sets out to examine a shared cross-pathogen question: what are the common mechanisms by which chronic viral exposure drives incomplete or dysfunctional immunological memory, and can these be identified regardless of the specific virus involved? By focusing on how early immune evasion strategies influence longer-term memory trajectories — including the establishment of T cell exhaustion and the role of innate-adaptive crosstalk in sustaining these states — and by comparing mechanisms across infections, this collection aims to identify shared determinants of memory dysfunction and to reveal targets that may be relevant across multiple chronic viral settings. We welcome the submission of Original Research, Review, Mini Review, Systematic Review, Perspective, Hypothesis and Theory, and Opinion articles addressing topics including, but not limited to: - Tissue-resident memory T cell (TRM) dynamics in the context of chronic viral infection and post-infection immune remodeling- Mucosal and tissue-compartment immune alterations in HBV, HCV, HIV, EBV, CMV, and SARS-CoV-2 infection- Innate-adaptive immune crosstalk and innate immune memory (trained immunity) in chronic viral settings- Comparative analysis of memory and exhaustion fate decisions across different chronic viral infections- B cell memory subset remodeling and humoral immune dysfunction in chronic infection- Common determinants of incomplete or dysfunctional immune memory restoration following viral control- Epigenetic and metabolic programming of exhausted and memory T cell states during persistent antigen exposure- Comparative analysis of CMV-driven immune alterations and immunosenescence alongside other chronic viral modelsStudies focusing exclusively on clinical management, pharmacology without immunological mechanistic evaluation, or descriptive virology lacking host immune analysis are out of scope. Topic editors: Mohamed Mahdi, Pradeep D Uchil Source: https://www.frontiersin.org/research-topics/85970/persistent-immune-remodeling-after-chronic-viral-infection