What this means
Neurotropic herpesviruses establish lifelong latency within the human nervous system. Traditionally viewed as either harmless latent infections or rare causes of acute encephalitis, growing evidence suggests these viruses undergo recurrent, subclinical reactivations throughout life.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Earlier studies
- Kind of research
- A summary of earlier studies
The science
- Original title
- Neurotropic herpesviruses as accelerators of brain aging: The role of latency and reactivation in neurodegeneration.
- Authors
- Nadholta P, Volety I, Shukla D
- Journal
- Virology
- Published
- Oct 27, 2026
- Study type
- Review
- PMID
- 42945857 ↗
Abstract
Neurotropic herpesviruses establish lifelong latency within the human nervous system. Traditionally viewed as either harmless latent infections or rare causes of acute encephalitis, growing evidence suggests these viruses undergo recurrent, subclinical reactivations throughout life. This review summarizes recent advances and introduces the multiple-hit viral reactivation model, proposing that repeated silent reactivation events act as cumulative biological stressors that accelerate brain aging. We describe a self-reinforcing cycle in which age-related immunosenescence impairs control of viral latency, leading to recurrent subclinical reactivation, chronic neuroinflammation, cellular senescence, and progressive disruption of central nervous system homeostasis. Rather than directly causing neurodegenerative disease, recurrent host-virus interactions gradually diminish brain resilience and promote the accumulation of pathogenic protein aggregates, including amyloid-β, tau, α-synuclein, and TDP-43. Clinical neurodegeneration emerges when the cumulative burden of lifelong viral reactivation exceeds the aging brain's capacity to maintain homeostasis. Recognizing herpesviruses as modifiable drivers of brain aging identifies subclinical viral reactivation as a key therapeutic target for preventing cognitive decline.
Nadholta P, Volety I, Shukla D Neurotropic herpesviruses as accelerators of brain aging: The role of latency and reactivation in neurodegeneration. Virology. 2026. doi:10.1016/j.virol.2026.111113. PMID: 42945857. https://pubmed.ncbi.nlm.nih.gov/42945857/