title: Viral genome silencing by neuronal sirtuin 1.
abstract: 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.
authors.affiliation: Program in Neuroscience, The State University of New York at Buffalo, 102 Farber Hall, 3435 Main Street, Buffalo, NY 14214, USA.
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Picchione
authors.forename: Arin
authors.initials: A
authors.lastname: Bhattacharjee
mesh_terms: D000256:Adenoviridae / Q000187:drug effects / Q000502:physiology; D000257:Adenoviridae Infections / Q000821:virology*; D000375:Aging; D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D004622:Embryo, Mammalian / Q000166:cytology / Q000201:enzymology / Q000821:virology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005453:Fluorescence; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000201:enzymology / Q000821:virology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D016679:Genome, Viral; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D009243:NAD / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000166:cytology / Q000201:enzymology* / Q000821:virology*; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D014161:Transduction, Genetic; D014775:Virus Activation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D011993:Recombinant Fusion Proteins; D009243:NAD; D056564:Sirtuin 1