Broad-spectrum antiviral effect of MoringaA-loaded exosomes against IAV by mediating the GCN5-TFEB-autolysosome pathway.
J Med Virol
; 96(9): e29906, 2024 Sep.
Article
em En
| MEDLINE
| ID: mdl-39262090
ABSTRACT
Influenza virus-induced viral pneumonia is a major threat to human health, and specific therapeutic agents for viral pneumonia are still lacking. MoringaA (MA) is an anti-influenza virus active compound isolated from Moringa seeds, which can inhibit influenza virus by activating the TFEB-autophagic lysosomal pathway in host cells. In this study, we obtained exosomes from M2-type macrophages and encapsulated and delivered MA (MA-Exos), and we investigated the efficacy of MA-Exos in antiviral and viral pneumonia in vivo and in vitro, respectively. In addition, we provided insights into the mechanism by which MA-Exos regulates TFEB-lysosomal autophagy by RNA sequencing. The MA-Exos showed broad-spectrum inhibition of IAV, and significant promotion of the autophagic lysosomal pathway. Meanwhile, we found that GCN5 gene and protein were significantly down-regulated in IAV-infected cells after MA-Exos intervention, indicating its blocking the acetylation of TFEB by GCN5. In addition, MA-Exos also significantly promoted autophagy in lung tissue cells of mice with viral pneumonia. MA-Exos can inhibit and clear influenza virus by mediating the TFEB-autophagy lysosomal pathway by a mechanism related to the down-regulation of histone acetyltransferase GCN5. Our study provides a strategy for targeting MA-Exos for the treatment of viral pneumonia from both antiviral and virus-induced inflammation inhibition pathways.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Vírus da Influenza A
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Autofagia
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos
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Exossomos
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Lisossomos
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Med Virol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
Estados Unidos