Cultured vestibular ganglion neurons demonstrate latent HSV1 reactivation

• Published in: The Laryngoscope Vol. 121; no. 10; p. 2268
• Main Authors: Roehm, Pamela C, Camarena, Vladimir, Nayak, Shruti, Gardner, James B, Wilson, Angus, Mohr, Ian, Chao, Moses V
• Format: Journal Article
• Language: English
• Published: United States 01.10.2011
• Subjects: Animals; Animals, Newborn; Cells, Cultured; Disease Models, Animal; DNA Replication; Fluorescent Antibody Technique; Herpes Simplex - physiopathology; Herpesvirus 1, Human - physiology; In Situ Hybridization, Fluorescence; In Vitro Techniques; Random Allocation; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Vestibular Nerve - cytology; Vestibular Nerve - physiology; Vestibular Nerve - virology; Vestibular Neuronitis - physiopathology; Virus Latency - physiology; Virus Replication - physiology
• DOI: 10.1002/lary.22035

Vestibular neuritis is a common cause of both acute and chronic vestibular dysfunction. Multiple pathologies have been hypothesized to be the causative agent of vestibular neuritis; however, whether herpes simplex type I (HSV1) reactivation occurs within the vestibular ganglion has not been demonstrated previously by experimental evidence. We developed an in vitro system to study HSV1 infection of vestibular ganglion neurons (VGNs) using a cell culture model system. basic science study. Lytic infection of cultured rat VGNs was observed following low viral multiplicity of infection (MOI). Inclusion of acyclovir suppressed lytic replication and allowed latency to be established. Upon removal of acyclovir, latent infection was confirmed with reverse-transcription polymerase chain reaction and by RNA fluorescent in situ hybridization for the latency-associated transcript (LAT). A total of 29% cells in latently infected cultures were LAT positive. The lytic ICP27 transcript was not detected by reverse-transcription polymerase chain reaction (RT-PCR). Reactivation of HSV1 occurred at a high frequency in latently infected cultures following treatment with trichostatin A (TSA), a histone deactylase inhibitor. VGNs can be both lytically and latently infected with HSV1. Furthermore, latently infected VGNs can be induced to reactivate using TSA. This demonstrates that reactivation of latent HSV1 infection in the vestibular ganglion can occur in a cell culture model, and suggests that reactivation of HSV1 infection a plausible etiologic mechanism of vestibular neuritis.