Targeting Viral Proteostasis Limits Influenza Virus, HIV, and Dengue Virus Infection.
Immunity
; 44(1): 46-58, 2016 Jan 19.
Article
em En
| MEDLINE
| ID: mdl-26789921
ABSTRACT
Viruses are obligate parasites and thus require the machinery of the host cell to replicate. Inhibition of host factors co-opted during active infection is a strategy hosts use to suppress viral replication and a potential pan-antiviral therapy. To define the cellular proteins and processes required for a virus during infection is thus crucial to understanding the mechanisms of virally induced disease. In this report, we generated fully infectious tagged influenza viruses and used infection-based proteomics to identify pivotal arms of cellular signaling required for influenza virus growth and infectivity. Using mathematical modeling and genetic and pharmacologic approaches, we revealed that modulation of Sec61-mediated cotranslational translocation selectively impaired glycoprotein proteostasis of influenza as well as HIV and dengue viruses and led to inhibition of viral growth and infectivity. Thus, by studying virus-human protein-protein interactions in the context of active replication, we have identified targetable host factors for broad-spectrum antiviral therapies.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
/
Replicação Viral
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Interações Hospedeiro-Parasita
/
Modelos Teóricos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Immunity
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos