SIRT1 remodels astrocyte metabolism and promotes viral replication during neurotropic orthoflavivirus infection
Angel, J. P.; Alzate, D.; Lindman, M.; Atkins, C.; Daniels, B. P.
Show abstract
Orthoflaviviruses depend on host metabolic resources to replicate, but how distinct cell types in the central nervous system (CNS) alter their metabolism in response to infection remains incompletely understood. Here, we examined whether the NAD+-dependent deacetylase SIRT1 is engaged during Zika virus (ZIKV) and West Nile virus (WNV) infection and whether its activity influences infection outcomes. SIRT1 activity increased in astrocytes isolated from infected mouse brains and in infected primary human astrocytes, but not in neurons or CNS myeloid cells. In astrocytes, infection induced transcriptomic, metabolomic, and functional changes consistent with SIRT1 activation, enhanced NAD+ salvage, and enhanced oxidative metabolism. Pharmacologic inhibition of SIRT1 or NAD+ salvage reduced ZIKV replication in astrocytes, whereas SIRT1 activation or supplementation with an NAD+ precursor increased replication. In mice, SIRT1 inhibition or nicotinamide (NAM) treatment reduced viral burden and mortality following ZIKV and WNV infection, while SIRT1 activation worsened disease. Together, these findings identify NAD+/SIRT1 as key regulators of cellular metabolism in infected astrocytes and support a role for this pathway in promoting orthoflavivirus replication and pathogenesis.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Zika virus infects pericytes in the choroid plexus and enters the central nervous system through the blood-cerebrospinal fluid barrier. 96%
- {-}{-}{-}{-}{-}{-}{-}{-}RNA structures within Venezuelan equine encephalitis virus E1 alter macrophage replication fitness and contribute to viral emergence 95%
- Mitochondrial Hyperactivity and Reactive Oxygen Species Drive Innate Immunity to the Yellow Fever Virus-17D Live-Attenuated Vaccine 95%
Similar papers in this journal
- Autophagy-Mediated Downregulation of AXL and TIM-1 Promotes Sustained Zika Virus Infection 96%
- MDA5 ISGylation is crucial for immune signaling to control viral replication and pathogenesis 95%
- Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex 94%
Similar papers in this journal
- Human endogenous retrovirus HERV-K(HML-2) RNA causes neurodegeneration through Toll-like receptors 95%
- Chikungunya virus infection disrupts lymph node lymphatic endothelial cell composition and function via MARCO 95%
- Disruption of innate defense responses by endoglycosidase HPSE promotes cell survival 94%
Similar papers in this journal
- Caspase-mediated regulation and cellular heterogeneity of the cGAS/STING pathway in Kaposi's sarcoma-associated herpesvirus infection 95%
- HCMV promotes viral reactivation through the coordinated regulation of Notch signaling by UL8 and miR-UL36 94%
- Single-genome analysis reveals heterogeneous association of the Herpes Simplex Virus genome with H3K27me2 and the reader PHF20L1 following infection of human fibroblasts 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.