Starvation after infection restricts enterovirus D68 replication.
Autophagy
; 19(1): 112-125, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-35446171
ABSTRACT
Enterovirus D68 (EV-D68) is a respiratory pathogen associated with acute flaccid myelitis, a childhood paralysis disease. No approved vaccine or antiviral treatment exists against EV-D68. Infection with this virus induces the formation of autophagosomes to enhance its replication but blocks the downstream autophagosome- lysosome fusion steps. Here, we examined the impact of autophagy induction through starvation, either before (starvation before infection, SBI) or after (starvation after infection, SAI) EV-D68 infection. We showed that SAI, but not SBI, attenuated EV-D68 replication in multiple cell lines and abrogated the viral-mediated cleavage of host autophagic flux-related proteins. Furthermore, SAI induced autophagic flux during EV-D68 replication and prevented production of virus-induced membranes, which are required for picornavirus replication. Pharmacological inhibition of autophagic flux during SAI did not rescue EV-D68 titers. SAI had the same effect in multiple cell types, and restricted the replication of several medically relevant picornaviruses. Our results highlight the significance of autophagosomes for picornavirus replication and identify SAI as an attractive broad-spectrum anti-picornavirus strategy.Abbreviations BAF bafilomycin A1; CCCP carbonyl cyanide m-chlorophenylhydrazone; CQ chloroquine; CVB3 coxsackievirus B3; EV-D68 enterovirus D68; hpi hour post-infection; MAP1LC3/LC3 microtubule associated protein 1 light chain 3; MOI multiplicity of infection; NSP2B nonstructural protein 2B; PV poliovirus; RES resveratrol; RV14 rhinovirus 14; SAI starvation after infection; SBI starvation before infection; SNAP29 synaptosome associated protein 29; SQSTM1/p62 sequestosome 1; TFEB transcription factor EB.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Enterovirus Humano D
/
Infecções por Enterovirus
/
Mielite
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Autophagy
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos