Strategic latency with temporal mutualism: a coevolutionary model of the host–varicella-zoster virus relationship

After primary infection with varicella, varicella-zoster virus (VZV) establishes a latent state that precedes the clinical manifestation of herpes zoster. Growing evidence, however, indicates that latency is not merely quiescent but represents an active immunological adaptation. We propose the <i>immunosensor hypothesis</i>, in which VZV latency within sensory ganglia contributes to host immune surveillance while simultaneously ensuring viral persistence. Using a game-theoretical framework, we conceptualize this interaction as a temporally partitioned evolutionarily stable strategy (TP-ESS). In this model, VZV progresses through three sequential phases across the host lifespan: (i) aggressive replication and transmission during primary infection, (ii) immunomodulatory latency during immune competence, and (iii) reactivation during immune decline. Each phase represents a dynamic equilibrium shaped by host immunity and viral life-history trade-offs. The TP-ESS framework integrates viral ecology, innate immunity, and neurovirology into a unified model of latency and reactivation, providing a conceptual basis for epidemiological patterns of herpes zoster and generating testable predictions on immunity-dependent viral behavior and host-virus coadaptation.