Injuries and Mechanisms Causing HSV1 Reactivation in Peripheral Neurons

Abstract

Objectives:

Herpes simplex type 1 (HSV1) reactivation in sensory neurons may underlie a number of idiopathic head and neck syndromes, including Bell’s palsy and delayed facial palsy following traumatic injury. In this study we first measured whether modeled surgical nerve injury (hypoxia and heat) reactivated HSV1 in neurons harvested from different ganglia (geniculate, vestibular, trigeminal, and sympathetic). We also measured the phosphorylation status of mTOR pathway proteins in conditions that either did or did not cause HSV1 reactivation.

Methods:

Basic/translation science study of cultured neurons latently infected with HSV1. Primary neuronal cultures were either kept under hypoxic conditions or heated to 43°C for 2 hours to simulate intraoperative neuronal injury. Outcome measures included HSV1 reactivation measured by expression of green fluorescent protein under HSV1 promoter and HSV1 viral titers. Other outcome measures included measurement of phosphorylation of mTOR1, S6, and S6kinase by western blot and immunofluorescent microscopy.

Results:

All latently infected neurons demonstrated HSV1 reactivation following hypoxia. Trigeminal, vestibular, and geniculate neurons demonstrated brisk HSV1 reactivation after heat treatment, but sympathetic neurons did not. All conditions leading to HSV1 reactivation significantly affected phosphorylation status of mTOR pathway proteins.

Conclusions:

Conditions which reactivate latent HSV1 lead to changes in phosphorylation of mTOR pathway proteins. Conditions that do not lead to HSV1 reactivation do not affect the mTOR pathway.