HHV-6A is a neurotropic herpesvirus able to infect several CNS cells including astrocytes and primary neurons. Here we found that HHV-6A infection of astrocytoma cells, by reducing autophagy, increased ROS and induced ER stress, promoting the release of inflammatory cytokines such as IL-6 and IL-1β and activating pathways such as STAT3, NF-kB and mTOR. Moreover, HHV-6A infection increased the production of CXCL13, a B lymphocyte attracting chemokine, whose recruitment in the CNS could further enhance neuroinflammation. Interestingly, HHV-6A also increased the release of cathepsin S by infected astrocytoma cells as well as by primary neurons. As this enzyme is involved in the degradation of MBP, this effect could contribute to the onset/progression of MS, a neurodegenerative disease that, besides inflammation, is characterized by a progressive demyelination process. In conclusion, this study unveils new molecular mechanisms through which HHV-6A may promote important aspects involved in several neurodegenerative diseases.

The dysregulation of autophagy and ER stress induced by HHV-6A infection activates pro-inflammatory pathways and promotes the release of inflammatory cytokines and cathepsin S by CNS cells / Romeo, M. A.; Gilardini Montani, M. S.; Benedetti, R.; Arena, A.; Gaeta, A.; Cirone, M.. - In: VIRUS RESEARCH. - ISSN 0168-1702. - 313:(2022), pp. 1-9. [10.1016/j.virusres.2022.198726]

The dysregulation of autophagy and ER stress induced by HHV-6A infection activates pro-inflammatory pathways and promotes the release of inflammatory cytokines and cathepsin S by CNS cells

Romeo M. A.;Gilardini Montani M. S.;Benedetti R.;Arena A.;Gaeta A.;Cirone M.
2022

Abstract

HHV-6A is a neurotropic herpesvirus able to infect several CNS cells including astrocytes and primary neurons. Here we found that HHV-6A infection of astrocytoma cells, by reducing autophagy, increased ROS and induced ER stress, promoting the release of inflammatory cytokines such as IL-6 and IL-1β and activating pathways such as STAT3, NF-kB and mTOR. Moreover, HHV-6A infection increased the production of CXCL13, a B lymphocyte attracting chemokine, whose recruitment in the CNS could further enhance neuroinflammation. Interestingly, HHV-6A also increased the release of cathepsin S by infected astrocytoma cells as well as by primary neurons. As this enzyme is involved in the degradation of MBP, this effect could contribute to the onset/progression of MS, a neurodegenerative disease that, besides inflammation, is characterized by a progressive demyelination process. In conclusion, this study unveils new molecular mechanisms through which HHV-6A may promote important aspects involved in several neurodegenerative diseases.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/1627726
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