Viral genome silencing by neuronal sirtuin 1

Neurotropic viruses remain dormant in sensory neurons for years, but upon reactivation, they can produce multiple disease states including pain symptoms. Latent viral DNA is extrachromosomal, maintained as a circular episome bound to histones. Here, we show the regulation of an adenoviral genome by the nicotinamide adenine dinucleotide (NAD⁺)-dependent histone deacetylator Sirt1 in dorsal root ganglion neurons. Pharmacological modulation of Sirt1 and Sirt1 overexpression both affected viral transgene expression. We propose that age or stressrelated neuronal NAD⁺ depletion may be a trigger for viral reactivation.