Inducing the Localization of HSP70 to Lipid Rafts by Borna Disease Virus 1 Promotes Its Invasion and Host Cells Apoptosis
Abstract The Borna disease virus 1 (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. Increasing evidence of human infections by BoDV-1 has highlighted the importance of antiviral drugs against BoDV-1. However, the process of BoDV-1 infection and its pathogenic mechanism remain elusive and there are few drugs targeting BoDV-1 infection. Our previous research suggests that BoDV-1 infects cells through lipid-related pathways. Heat shock protein 70 (HSP70) in lipid rafts (LR) has been identified to participate in various viral infections. In this study, we reported that the LR-HSP70-Caspase-3 axis engages BoDV-1 invasion and host cell apoptosis. Mechanistically, the LR inhibitor, Methyl-β-cyclodextrin (MβCD), interferes the localization HSP70 to LR and prevents BoDV-1 entry without reducing cell viability.Furthermore, we confirmed that the HSP70 is recruited into LR after BoDV-1 invasion by HSP70 knockdown and overexpression assays. And the migration of HSP70 to LR weakened the interaction between HSP70 and Caspase-3, which reducing the chaperone protective ability of HSP70 to Caspase-3, increasing the intracellular active Caspase-3 and promoting host cell apoptosis. Importantly, the MβCD treatment can effectively alleviate the symptoms and pathological changes in a model of BoDV-1 encephalitis, suggesting a significant antiviral effect in vivo. Our report reveals the process of BoDV-1 invasion and the mechanisms by which MβCD inhibits the infection, offering potential guidance for the development in the targeted treatment of BoDV-1 infection..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 27. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lei, Yang [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-3808348/v1 |
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| PPN (Katalog-ID): |
XRA042023270 |
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| 245 | 1 | 0 | |a Inducing the Localization of HSP70 to Lipid Rafts by Borna Disease Virus 1 Promotes Its Invasion and Host Cells Apoptosis |
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| 520 | |a Abstract The Borna disease virus 1 (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. Increasing evidence of human infections by BoDV-1 has highlighted the importance of antiviral drugs against BoDV-1. However, the process of BoDV-1 infection and its pathogenic mechanism remain elusive and there are few drugs targeting BoDV-1 infection. Our previous research suggests that BoDV-1 infects cells through lipid-related pathways. Heat shock protein 70 (HSP70) in lipid rafts (LR) has been identified to participate in various viral infections. In this study, we reported that the LR-HSP70-Caspase-3 axis engages BoDV-1 invasion and host cell apoptosis. Mechanistically, the LR inhibitor, Methyl-β-cyclodextrin (MβCD), interferes the localization HSP70 to LR and prevents BoDV-1 entry without reducing cell viability.Furthermore, we confirmed that the HSP70 is recruited into LR after BoDV-1 invasion by HSP70 knockdown and overexpression assays. And the migration of HSP70 to LR weakened the interaction between HSP70 and Caspase-3, which reducing the chaperone protective ability of HSP70 to Caspase-3, increasing the intracellular active Caspase-3 and promoting host cell apoptosis. Importantly, the MβCD treatment can effectively alleviate the symptoms and pathological changes in a model of BoDV-1 encephalitis, suggesting a significant antiviral effect in vivo. Our report reveals the process of BoDV-1 invasion and the mechanisms by which MβCD inhibits the infection, offering potential guidance for the development in the targeted treatment of BoDV-1 infection. | ||
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| 700 | 1 | |a Xu, Xiaoyan |4 aut | |
| 700 | 1 | |a Tan, Qing |4 aut | |
| 700 | 1 | |a Xiang, Yayun |4 aut | |
| 700 | 1 | |a Tan, Tingting |4 aut | |
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| 700 | 1 | |a Xie, Peng |4 aut | |
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