Latent Viral Reactivation and Immune Aging

Lifelong viral infections can quietly alter the immune system, with effects that persist over the time. Viruses such as the ones from Herpesviridae family persist despite immune surveillance and often reactivate as immunity declines with age. CMV is particularly linked to immune remodeling, including the expansion of highly differentiated CD8⁺ T cells (Tem, Temra), often expressing senescence-associated markers (KLRG1, CD57, CD27⁻CD28⁻). Similar changes occur with EBV and HSV infection under suppression. These shifts extend beyond T cells, involving NK cells, γδ T cells, and NKT cells, reflecting broad effects on adaptive and innate immunity. Such remodeling contributes to immunosenescence and may exacerbate age-related disease risk.

The goal of this research topic is to systematically define how lifelong latent infections, particularly CMV, EBV, HSV shape immune aging across multiple lymphocyte compartments. Specifically, it aims to identify virus-associated changes at phenotypic and functional levels, including shifts in differentiation, activation, exhaustion, and cytotoxicity. Despite substantial progress, many aspects of virus-driven immune remodeling remain unclear. How do epigenetic and chromatin modifications induced by latent viral infections influence immune cell function and differentiation with age? What are the tissue-specific patterns of immune remodeling during chronic viral infections and aging? How do EBV, HSV, and CMV differ in their effects on the aging immune system? What are the links between latent viral infections and the development of age-related diseases? High-dimensional multiomics approaches, including scRNA-seq, CITE-seq, ATAC-seq, TCR/BCR-seq, and multiplex flow cytometry, can be used to map the interactions between viral serostatus, age, and immune cell remodeling. Ultimately, the research topic seeks to uncover biomarkers of virus-driven immune remodeling and generate functional insights to guide interventions that preserve immune competence during aging.

We welcome submissions addressing:

• Virus-associated immune remodeling with age, particularly during EBV, HSV, and other less-characterized chronic latent infections, with comparisons to CMV-related findings.
• Epigenetic and chromatin modifications in adaptive and innate immune cells driven by chronic viral infection coupled with aging.
• Functional consequences of viral seropositivity, including changes in cytotoxicity, activation, and exhaustion.
• Co-infections and their combined impact on immune system heterogeneity and immunosenescence.
• Health consequences of latent viral infection and their connection to age-related diseases
• T and B cell repertoire remodeling in the context of chronic viral infections and aging.
• Immune cell remodeling in tissues during chronic viral infections coupled with aging.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: chronic infection, herpesviruses, CMV, reactivation, aging, lymphocytes

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.