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Herpes simplex encephalitis is linked with selective mitochondrial damage; a post-mortem and in vitro study

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dc.contributor.authorMałgorzata Wnęken_US
dc.contributor.authorLorenzo Resselen_US
dc.contributor.authorEmanuele Riccien_US
dc.contributor.authorCarmen Rodriguez-Martinezen_US
dc.contributor.authorJulio Cesar Villalvazo Guerreroen_US
dc.contributor.authorZarini Ismailen_US
dc.contributor.authorColin Smithen_US
dc.contributor.authorAnja Kiparen_US
dc.contributor.authorBeate Sodeiken_US
dc.contributor.authorPatrick F Chinneryen_US
dc.contributor.authorTom Solomonen_US
dc.contributor.authorMichael J Griffithsen_US
dc.date.accessioned2024-05-27T15:07:34Z
dc.date.available2024-05-27T15:07:34Z
dc.date.issued2016
dc.description.abstractHerpes simplex virus type-1 (HSV-1) encephalitis (HSE) is the most commonly diagnosed cause of viral encephalitis in western countries. Despite antiviral treatment, HSE remains a devastating disease with high morbidity and mortality. Improved understanding of pathogenesis may lead to more effective therapies. Mitochondrial damage has been reported during HSV infection in vitro. However, whether it occurs in the human brain and whether this contributes to the pathogenesis has not been fully explored. Minocycline, an antibiotic, has been reported to protect mitochondria and limit brain damage. Minocycline has not been studied in HSV infection. In the first genome-wide transcriptomic study of post-mortem human HSE brain tissue, we demonstrated a highly preferential reduction in mitochondrial genome (MtDNA) encoded transcripts in HSE cases (n = 3) compared to controls (n = 5). Brain tissue exhibited a significant inverse correlation for immunostaining between cytochrome c oxidase subunit 1 (CO1), a MtDNA encoded enzyme subunit, and HSV-1; with lower abundance for mitochondrial protein in regions where HSV-1 was abundant. Preferential loss of mitochondrial function, among MtDNA encoded components, was confirmed using an in vitro primary human astrocyte HSV-1 infection model. Dysfunction of cytochrome c oxidase (CO), a mitochondrial enzyme composed predominantly of MtDNA encoded subunits, preceded that of succinate dehydrogenase (composed entirely of nuclear encoded subunits). Minocycline treated astrocytes exhibited higher CO1 transcript abundance, sustained CO activity and cell viability compared to non-treated astrocytes. Based on observations from HSE patient tissue, this study highlights mitochondrial damage as a critical and early event during HSV-1 infection. We demonstrate minocycline preserves mitochondrial function and cell viability during HSV-1 infection. Minocycline, and mitochondrial protection, offers a novel adjunctive therapeutic approach for limiting brain cell damage and potentially improving outcome among HSE patients.en_US
dc.identifier.doi10.1007/s00401-016-1597-2
dc.identifier.epage451
dc.identifier.issn1432-0533
dc.identifier.issue3
dc.identifier.spage433
dc.identifier.urihttps://link.springer.com/article/10.1007%2Fs00401-016-1597-2
dc.identifier.urihttps://oarep.usim.edu.my/handle/123456789/4175
dc.identifier.volume132
dc.language.isoen_USen_US
dc.publisherSpringer Nature Switzerland AGen_US
dc.relation.ispartofActa Neuropathologicaen_US
dc.subjectGene-expression; Herpes simplex virus encephalitis; Human; Minocycline; Mitochondriaen_US
dc.titleHerpes simplex encephalitis is linked with selective mitochondrial damage; a post-mortem and in vitro studyen_US
dc.typeArticleen_US
dspace.entity.typePublication

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