Modulation of Voltage-Gated Sodium Channel Activity in Human Dorsal Root Ganglion Neurons by Herpesvirus Quiescent Infection

• DOI: 10.1128/jvi.01823-19
• Publication Date: 2019-11-06T11:19:26Z
• Authors: Qiaojuan Zhang; Miguel Martin-Car...; S. Victor Hsia
• Keywords: Pseudorabies; Dorsal root ganglion; Postherpetic Neuralgia

The molecular mechanisms of pain associated with alphaherpesvirus latency are not clear. We hypothesize that the voltage-gated sodium channels (VGSC) on dorsal root ganglion (DRG) neurons controlling electrical impulses may have abnormal activity during latent viral infection and reactivation. used herpes simplex virus 1 (HSV-1) to infect human DRG-derived neuronal cell line HD10.6 in order study establishment maintenance latency, reactivation, changes functional expression VGSCs. Differentiated cells exhibited robust tetrodotoxin (TTX)-sensitive currents, acute significantly reduced VGSCs within 24 h completely abolished VGSC 3 days. A quiescent state mimicking can be achieved presence acyclovir (ACV) for 7 days followed by 5 ACV washout, then viruses remain dormant another weeks. It was noted HSV-1 loss caused could blocked treatment. However, continued treatment 4 showed a gradual recovery expression. Furthermore, latently infected higher than controls. overall regulation proved increased transcription possible translation Nav1.7. Together, these observations demonstrated very complex pattern electrophysiological HSV DRG neurons, which implications understanding virus-mediated linked reactivation.IMPORTANCE reactivation herpesviruses, most commonly varicella-zoster (VZV) pseudorabies (PRV), cause cranial nerve disorder unbearable pain. Clinical studies also reported causes postherpetic neuralgia chronic occipital humans. current work meticulously profile processes using ganglion-derived as an vitro model. Our results indicated eliminated upon but steadily recovered even activity. This finding advances our knowledge how generate uncharacteristic due influenced virus.