Recurrent Herpes Simplex Virus Type 1 (HSV-1) Infection Modulates Neuronal Aging Marks in In Vitro and In Vivo Models |
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Authors: | Giorgia Napoletani Virginia Protto Maria Elena Marcocci Lucia Nencioni Anna Teresa Palamara Giovanna De Chiara |
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Affiliation: | 1.Department of Public Health and Infectious Diseases, Sapienza University of Rome, Laboratory Affiliated to Istituto Pasteur Italia–Fondazione Cenci Bolognetti, 00185 Rome, Italy; (G.N.); (V.P.); (M.E.M.); (L.N.); (A.T.P.);2.Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy;3.Institute of Translational Pharmacology, National Research Council (CNR), 00133 Rome, Italy |
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Abstract: | Herpes simplex virus 1 (HSV-1) is a widespread neurotropic virus establishing a life-long latent infection in neurons with periodic reactivations. Recent studies linked HSV-1 to neurodegenerative processes related to age-related disorders such as Alzheimer’s disease. Here, we explored whether recurrent HSV-1 infection might accelerate aging in neurons, focusing on peculiar marks of aged cells, such as the increase in histone H4 lysine (K) 16 acetylation (ac) (H4K16ac); the decrease of H3K56ac, and the modified expression of Sin3/HDAC1 and HIRA proteins. By exploiting both in vitro and in vivo models of recurrent HSV-1 infection, we found a significant increase in H4K16ac, Sin3, and HDAC1 levels, suggesting that the neuronal response to virus latency and reactivation includes the upregulation of these aging markers. On the contrary, we found a significant decrease in H3K56ac that was specifically linked to viral reactivation and apparently not related to aging-related markers. A complex modulation of HIRA expression and localization was found in the brain from HSV-1 infected mice suggesting a specific role of this protein in viral latency and reactivation. Overall, our results pointed out novel molecular mechanisms through which recurrent HSV-1 infection may affect neuronal aging, likely contributing to neurodegeneration. |
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Keywords: | HSV-1 Herpes simplex virus recurrent infection neuronal aging histone modifications |
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