Varicella-Zoster virus infected human neurons are resistant to apoptosis

Kennedy, P. G.E., Graner, M. W., Gunaydin, D., Bowlin, J., Pointon, T. and Yu, X. (2020) Varicella-Zoster virus infected human neurons are resistant to apoptosis. Journal of Neurovirology, 26, pp. 330-337. (doi: 10.1007/s13365-020-00831-6) (PMID:32125664)

Abstract

Varicella-zoster virus (VZV) is a pathogenic human herpesvirus that causes varicella (chickenpox) as a primary infection following which it becomes latent in ganglionic neurons. Following viral reactivation many years later VZV causes herpes zoster (shingles) as well as a variety of other neurological syndromes. The molecular mechanisms of the conversion of the virus from a lytic to a latent state in ganglia are not well understood. In order to gain insights into the neuron-virus interaction, we studied virus-induced apoptosis in cultures of both highly pure terminally differentiated human neurons and human fetal lung fibroblasts (HFL). It was found that (a) VZV DNA did not accumulate in infected human neurons; (b) VZV transcripts were present at lower levels at all days studied post-infection in neurons; (c) Western blot analysis showed less VZV IE 63 and very little detectable VZV gE proteins in infected neurons compared with HFL; (d) lower levels of the apoptotic marker cleaved Caspase-3 protein were detected in VZV-infected neurons compared with HFL, and higher levels of the known anti-apoptotic proteins Bcl2, Bcl-XL and also the mitochondrial MT-CO2 protein were found in VZV-infected neurons compared with uninfected cells; and (e) both the MT-CO2 protein and VZV IE 63-encoded protein were detected in infected neurons by dual immunofluorescence. These findings showed that neurons are resistant to VZV-induced apoptosis, which may have relevance to the switching of VZV from a lytic to latent ganglionic neuronal infection.

• Item Type: Articles
• Additional Information: This work was supported by Public Health Service grant AG006127 from the National Institutes of Health.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kennedy, Professor Peter
• Authors: Kennedy, P. G.E., Graner, M. W., Gunaydin, D., Bowlin, J., Pointon, T., and Yu, X.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Journal of Neurovirology
• Publisher: Springer
• ISSN: 1355-0284
• ISSN (Online): 1538-2443
• Published Online: 03 March 2020
• Copyright Holders: Copyright © 2020 Springer Nature
• First Published: First published in Journal of Neurovirology 26:330–337
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher