Cell-Mediated Immunity Cannot Eradicate VZV from Neurons—It Only Suppresses Reactivation
Cell-mediated immunity (CMI) does not eradicate varicella zoster virus from latently infected neurons; instead, it continuously suppresses viral reactivation throughout life. Once VZV establishes latency in sensory ganglia after primary infection, the virus persists permanently in neuronal cells, and CMI functions as an ongoing surveillance mechanism rather than an eradicating force 1.
The Nature of VZV Latency in Neurons
After primary varicella infection, VZV becomes permanently latent in cranial nerve ganglia, dorsal root ganglia, and autonomic ganglia along the entire neuraxis 2, 3.
The virus is not "hiding" from CMI in a passive sense—rather, it exists in a state of viral dormancy within neurons where viral gene expression is minimal and replication is suppressed 3.
The mechanisms controlling VZV latency are not fully understood, but the virus persists indefinitely in ganglionic neurons and cannot be eliminated by the immune system 1.
CMI as Continuous Suppression, Not Eradication
VZV-specific cell-mediated immunity maintains viral latency by continuously suppressing reactivation attempts, not by clearing the virus from infected neurons 3, 4.
When VZV-specific CMI declines—whether due to aging (immunosenescence), immunosuppressive therapy, or conditions like HIV—the virus reactivates and travels along nerve pathways to cause herpes zoster 5, 2.
The decline in zoster-specific cell-mediated immunity allows the latent virus in sensory ganglia to travel along nerve pathways, causing inflammation and nerve damage 5.
Evidence That CMI Cannot Eradicate Latent VZV
The lifetime risk of herpes zoster is 15-30% in the general population, demonstrating that even decades of intact CMI cannot eliminate latent virus 1, 5.
Studies show that interleukin-6 and type 1 interferons significantly reduce VZV transcription and viral spread in human neurons, but these cytokines suppress rather than eliminate the virus 6.
Even in immunocompetent individuals with robust CMI, VZV remains latent and capable of reactivation throughout life, proving that immune surveillance controls but does not eradicate the virus 3, 7.
Clinical Implications
The inability of CMI to eradicate latent VZV explains why vaccination strategies focus on boosting VZV-specific immunity to prevent reactivation rather than clearing established infection 1, 8.
Immunocompromised patients (those on high-dose corticosteroids ≥7.5 mg/day, JAK inhibitors, or with HIV) have dramatically increased herpes zoster rates because their weakened CMI can no longer adequately suppress viral reactivation 5.
The recombinant zoster vaccine (RZV) demonstrates 88.8% efficacy against postherpetic neuralgia by boosting specific T-cell production and VZV-specific immunity, not by eliminating latent virus 9.
Common Pitfalls to Avoid
Do not assume that a strong immune response after primary infection will eventually clear VZV from neurons—the virus establishes permanent latency that persists for life 2, 3.
Recognize that neurological complications from VZV reactivation (meningoencephalitis, myelitis, vasculopathy) can occur decades after primary infection, even in previously immunocompetent individuals, because CMI wanes with age 4, 7.
Understand that varicella vaccination does not prevent latency establishment—even vaccine-strain virus (Oka strain) can become latent and later reactivate, though at lower rates than wild-type virus 1.