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Open AccessArticle

Upregulation of miR-101 during Influenza A Virus Infection Abrogates Viral Life Cycle by Targeting mTOR Pathway

1
Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India
2
Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi 110067, India
3
School of Science, Monash University, Bandar Sunway 47500, Malaysia
*
Authors to whom correspondence should be addressed.
Viruses 2020, 12(4), 444; https://doi.org/10.3390/v12040444
Received: 10 February 2020 / Revised: 22 March 2020 / Accepted: 29 March 2020 / Published: 15 April 2020
(This article belongs to the Special Issue Influenza A Virus: Host-Virus Relationship)
Micro RNAs (miRNAs) are a class of small non-coding single-stranded RNA, which play an important role in modulating host-Influenza A virus (IAV) crosstalk. The interplay between influenza and miRNA interaction is defined by a plethora of complex mechanisms, which are not fully understood yet. Here, we demonstrate that in IAV infected A549 cells, a synchronous increase was observed in the expression of mTOR up to 24 hpi and significant downregulation at 48 hpi. Additionally, NP of IAV interacts with mTOR and modulates the levels of mTOR mRNA and protein, thus regulating the translation of host cell. RNA sequencing and qPCR analysis of IAV-infected A549 cells and NP transfected cells revealed that miR-101 downregulates mTOR transcripts at later stages of infection. Ectopic expression of miR-101 mimic led to a decrease in expression of NP, a reduction in IAV titer and replication. Moreover, treatment of the cells with Everolimus, a potent inhibitor of mTOR, resulted in an increase of miR-101 transcript levels, which further suppressed the viral protein synthesis. Collectively, the data suggest a novel mechanism that IAV stimulates mTOR pathway at early stages of infection; however, at a later time-point, positive regulation of miR-101 restrains the mTOR expression, and hence, the viral propagation. View Full-Text
Keywords: Influenza A virus; mTOR; micro RNA; cellular pathway; virus replication Influenza A virus; mTOR; micro RNA; cellular pathway; virus replication
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Sharma, S.; Chatterjee, A.; Kumar, P.; Lal, S.; Kondabagil, K. Upregulation of miR-101 during Influenza A Virus Infection Abrogates Viral Life Cycle by Targeting mTOR Pathway. Viruses 2020, 12, 444.

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