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

The International Journal of Biochemistry & Cell Biology
Ge LiuKaio Kitazato

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 autophag...Continue Reading

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Citations

May 28, 2016·Viruses·Valerie Le SageAndrew J Mouland
Jul 5, 2016·BioMed Research International·Zhen QinMingyuan Li
Jul 8, 2018·Molecular & Cellular Proteomics : MCP·Andrea C BeckerJörn Dengjel
Dec 14, 2018·Journal of Virology·Ruifang WangHongbo Zhou
Mar 13, 2019·Cells·Mariana MarquesDaniela Ribeiro
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May 1, 2018·Reviews in Medical Virology·Asghar AbdoliFaezeh Forouzanfar
Mar 1, 2018·Frontiers in Microbiology·Yupeng WangChan Ding
Apr 9, 2019·Veterinary Microbiology·Tianqi YuBoli Hu
Mar 10, 2021·Epigenomics·Bimal P JitAshok Sharma
Dec 31, 2021·Virulence·Ao ZhouBin Tang

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