Editor's Choice: Persistence of Varicella Zoster Virus DNA in Saliva After Herpes Zoster

Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus. Primary infection usually causes varicella (chicken pox), after which virus become latent in ganglionic neurons along the entire neuraxis [1, 2]. Reactivation decades later produces zoster (shingles) frequently followed by chronic pain (postherpetic neuralgia [PHN]), mostly in individuals >60 years old. The cause and pathogenesis of PHN are unknown. Two non–mutually exclusive theories are that (1) the excitability of ganglionic or even spinal cord neurons is altered, and (2) there is persistent productive virus infection in ganglia. Although virological analyses of ganglia demonstrating productive VZV infection from patients with PHN have not been conducted, evidence supporting the second theory comes from the detection of VZV DNA in peripheral blood mononuclear cells (PBMCs) of elderly patients with PHN for years after zoster [3], but not in PBMCs collected >38 days after zoster in patients who did not develop PHN [4]; these observations might reflect the acquisition of virus by mononuclear cells, particularly antigen-presenting cells, while trafficking through productively infected ganglia [5]. Further evidence of persistent productive infection in PHN has been provided by an open-label study reporting clinical improvement after intravenous acyclovir in 8 (53%) of 15 patients with PHN [6]. Active VZV infection can also be confirmed on the basis of the detection of VZV DNA in human saliva. VZV DNA was first detected in saliva of patients with Ramsay Hunt syndrome (facial paralysis and zoster oticus), including patients with facial paralysis who did not have rash [7]. VZV DNA was later found in saliva of stressed healthy astronauts [8] as well as in all of 54 patients with acute herpes zoster studied over a 3-week period [9]. To test whether VZV DNA might remain in the saliva of zoster patients with PHN for a longer time than in zoster patients who did not develop PHN, we analyzed saliva samples from individuals aged ≥60 years who had (1) a history of zoster but not PHN, (2) zoster and PHN, and (3) no history of zoster.