Back to Search
Start Over
Varicella zoster virus-induced autophagy in human neuronal and hematopoietic cells exerts antiviral activity.
- Source :
-
Journal of medical virology [J Med Virol] 2024 Jun; Vol. 96 (6), pp. e29690. - Publication Year :
- 2024
-
Abstract
- Autophagy is a degradational pathway with pivotal roles in cellular homeostasis and survival, including protection of neurons in the central nervous system (CNS). The significance of autophagy as antiviral defense mechanism is recognized and some viruses hijack and modulate this process to their advantage in certain cell types. Here, we present data demonstrating that the human neurotropic herpesvirus varicella zoster virus (VZV) induces autophagy in human SH-SY5Y neuronal cells, in which the pathway exerts antiviral activity. Productively VZV-infected SH-SY5Y cells showed increased LC3-I-LC3-II conversion as well as co-localization of the viral glycoprotein E and the autophagy receptor p62. The activation of autophagy was dependent on a functional viral genome. Interestingly, inducers of autophagy reduced viral transcription, whereas inhibition of autophagy increased viral transcript expression. Finally, the genotype of patients with severe ocular and brain VZV infection were analyzed to identify potential autophagy-associated inborn errors of immunity. Two patients expressing genetic variants in the autophagy genes ULK1 and MAP1LC3B2, respectively, were identified. Notably, cells of both patients showed reduced autophagy, alongside enhanced viral replication and death of VZV-infected cells. In conclusion, these results demonstrate a neuro-protective role for autophagy in the context of VZV infection and suggest that failure to mount an autophagy response is a potential predisposing factor for development of severe VZV disease.<br /> (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)
- Subjects :
- Humans
Autophagy-Related Protein-1 Homolog metabolism
Autophagy-Related Protein-1 Homolog genetics
Virus Replication
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins metabolism
Varicella Zoster Virus Infection virology
Viral Envelope Proteins genetics
Viral Envelope Proteins metabolism
Cell Line
Intracellular Signaling Peptides and Proteins metabolism
Intracellular Signaling Peptides and Proteins genetics
Host-Pathogen Interactions
Autophagy
Herpesvirus 3, Human physiology
Herpesvirus 3, Human pathogenicity
Neurons virology
Subjects
Details
- Language :
- English
- ISSN :
- 1096-9071
- Volume :
- 96
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of medical virology
- Publication Type :
- Academic Journal
- Accession number :
- 38804180
- Full Text :
- https://doi.org/10.1002/jmv.29690