Autophagy is involved in regulating influenza A virus RNA and protein synthesis associated with both modulation of Hsp90 induction and mTOR/p70S6K signaling pathway. (March 2016)

• Record Type: Journal Article
• Authors: Liu, Ge; Zhong, Meigong; Guo, Chaowan; Komatsu, Masaaki; Xu, Jun; Wang, Yifei; Kitazato, Kaio
• Is Part Of: International journal of biochemistry & cell biology. Volume 72(2016:Mar.)
• Page Start: 100
• Page End: 108
• Publication Date: 2016-03
• Subjects: IAV influenza A virus -- PGG 1, 2, 3, 4, 6-penta-O-galloyl-β-d-glucose -- MEF mouse embryonic fibroblast -- mTOR mammalian target of rapamycin -- Atg autophagy gene -- 4E-BP1 eukaryotic initiation factor 4E-binding protein 1 -- p70S6K p70 ribosomal protein S6 kinase; Autophagy -- Influenza A virus -- Viral RNA and protein synthesis -- Hsp90 -- mTOR signal pathway -- Pentagalloyl glucose; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2016.01.012
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Influenza A virus (IAV) infection triggers autophagosome formation, but inhibits the fusion of autophagosomes with lysosomes. However, the role of autophagy in IAV replication is still largely unclarified. In this study, we aim to reveal the role of autophagy in IAV replication and the molecular mechanisms underlying the regulation. By using autophagy-deficient (Atg7 −/− ) MEFs, we demonstrated that autophagy deficiency significantly reduced the levels of viral proteins, mRNA and genomic RNAs (vRNAs) without affecting viral entry. We further found that autophagy deficiency lead to a transient increase in phosphorylation of mTOR and its downstream targets including 4E-BP1 and S6 at a very early stage of IAV infection, and markedly suppressed p70S6K phosphorylation at the late stage of IAV infection. Furthermore, autophagy deficiency resulted in impairment of Hsp90 induction in response to IAV infection. These results indicate that IAV regulates autophagy to benefit the accumulation of viral elements (synthesis of viral proteins and genomic RNA) during IAV replication. This regulation is associated with modulation of Hsp90 induction and mTOR/p70S6K signaling pathway. Our results provide important evidence for the role of autophagy in IAV replication and the mechanisms underlying the regulation.