Bik Mediates Caspase-Dependent Cleavage of Viral Proteins to Promote Influenza A Virus Infection.
Am J Respir Cell Mol Biol
; 54(5): 664-73, 2016 05.
Article
em En
| MEDLINE
| ID: mdl-26437021
ABSTRACT
Influenza virus induces apoptosis in infected cells to promote viral replication by manipulating the host cell death signaling pathway. Although some Bcl-2 family proteins play a role in the replication of influenza A virus (IAV), the role of cell death pathways in the viral replication cycle is unclear. We investigated whether deficiency of the proapoptotic Bcl-2 family protein, Bik, plays a role in IAV replication. IAV replication was attenuated in mouse airway epithelial cells (MAECs) from bik(-/-) compared with bik(+/+) mice, as indicated by reduced viral titers. Bik(-/-) MAECs showed more stable transepithelial resistance after infection than did bik(+/+) MAECs, were less sensitive to infection-induced cell death, and released fewer copies of viral RNA. Similar results were obtained when Bik expression was suppressed in human airway epithelial cells (HAECs). Bik(+/+) mice lost weight drastically and died within 8 days of infection, whereas 75% of bik(-/-) mice survived infection for 14 days and were 10-fold less likely to die from infection compared with bik(+/+) mice. IAV infection activated caspase 3 in bik(+/+) but not in bik(-/-) MAECs. Cleavage of viral nucleoprotein and M2 proteins were inhibited in bik(-/-) MAECs and when caspase activation was inhibited in HAECs. Furthermore, Bik deficiency impaired cytoplasmic export of viral ribonucleoprotein. These studies suggest a link between Bik-mediated caspase activation and cleavage of viral proteins. Thus, inhibition of proapoptotic host factors such as Bik and downstream mediators of cell death may represent a novel approach to influenza treatment.
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Base de dados:
MEDLINE
Assunto principal:
Vírus da Influenza A
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Proteínas Virais
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Infecções por Orthomyxoviridae
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Proteínas Mitocondriais
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas Reguladoras de Apoptose
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Influenza Humana
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Caspase 3
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Proteínas de Membrana
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article