Sirt1 Modulates Varicella Zoster Virus Replication in the Rat Dorsal Root Ganglion Neurons
MetadataShow full item record
Background: Varicella zoster virus (VZV) is the causative agent of chicken pox (varicella) during primary infection and herpes zoster (HZ) or shingles upon reactivation from latency. During primary infection, VZV establishes latency within the dorsal root ganglia (DRG) and in the trigeminal ganglia. Most studies indicate that neurons are the primary, if not the exclusive site of latent virus. Reactivation of VZV is frequently associated with symptoms ranging from discomfort to serious, long-lasting pain known as post-herpetic neuralgia (PHN). In the United States, the number of individuals suffering from HZ is estimated to be approximately 1 million people annually. Between 25 to 50% of these affected individuals will develop PHN VZV reactivation can also result in vasculopathy, myelopathy, and retinal necrosis. Our goals are to establish an in vitro VZV infection model to study viral activity and to investigate the effects of host Sirt1 activity on viral replication. Methods and Materials: Cultured rat embryonic DRG neurons and glia were infected by a VZV recombinant virus containing luciferase (pOka VZV-LUC) or a VZV recombinant virus containing green fluorescent protein (GFP) (pOka VZV-GFP). Cells were treated with Sirt1 activators and inhibitors starting at 24 hours post infection. GFP expression was used to visualize expression of VZV. The expression of luciferase was monitored by promega dual reporter luciferase assay via a plate reader. Results: Neurons treated with Sirt1 activators caused both a decrease in luciferase activity levels, indicating a decrease in viral replication and a decrease in GFP expression whereas when treated with the Sirt1 inhibitor, luciferase activity and GFP expression increased. Conclusion: Sirt1 regulates VZV infection and replication in neurons. An age dependent decline in Sirt1 activity may be the trigger for VZV reactivation. Demonstrating that Sirt1 has modulated viral replications may lead to novel treatments of HZ using Sirt1 activators.