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 stress-related neuronal NAD(+) depletion may be a trigger for viral reactivation.