miR-29a is a negative regulator of influenza virus infection through targeting of the frizzled 5 receptor
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ORIGINAL ARTICLE
miR‑29a is a negative regulator of influenza virus infection through targeting of the frizzled 5 receptor Xiaoyun Yang1,2 · Yurong Liang1,2 · Gayan Bamunuarachchi1,2 · Yanzhao Xu1,2 · Kishore Vaddadi1,2 · Samuel Pushparaj1,2 · Dao Xu1,2 · Zhengyu Zhu1,2 · Rachel Blaha2 · Chaoqun Huang1,2 · Lin Liu1,2 Received: 6 November 2019 / Accepted: 29 September 2020 © Springer-Verlag GmbH Austria, part of Springer Nature 2020
Abstract Influenza A virus (IAV) infections result in a large number of deaths and substantial economic losses each year. MicroRNAs repress gene expression and are involved in virus-host interactions. miR-29a is known to have anti-tumor and anti-fibrotic effects. However, the role of miR-29a in IAV infection is unclear. In the present study, we investigated the effect of miR-29a on IAV infection and the mechanisms by which it functions. IAV infection was found to cause decreased miR-29a expression in lung epithelial A549 cells and mouse lungs. Overexpression of miR-29a reduced IAV mRNA and protein levels and progeny virus production in HEK293 and A549 cells. Inhibition of IAV infection by miR-29a was observed with different strains of IAV, including A/PR/8/34, A/WSN/1933, and clinical isolates A/OK/3052/09 and A/OK/309/06 H3N2. Knockout of miR-29a using CRISPR/Cas9 resulted in an increase in viral mRNA and protein levels, confirming that miR-29a suppresses IAV infection. A 3’ untranslated region (3’-UTR) reporter assay showed that miR-29a had binding sites in the 3’-UTR of the Wnt-Ca2+ signaling receptor frizzled 5 gene, and overexpression of miR-29a reduced the level of the endogenous frizzled 5 protein. Wnt5a treatment of HEK293 and A549 cells enhanced IAV infection. Our results suggest that miR-29a inhibits IAV infection, probably via the frizzled 5 receptor.
Introduction Influenza A virus (IAV) is a human respiratory pathogen that causes disease of varying severity, from mild upper respiratory infection to severe pneumonia [1, 2]. IAV is a member of the family Orthomyxovirus and has an eightsegmented RNA genome that encodes a limited number of proteins. Thus, IAV has to utilize a wide array of host factors for its replication, from binding to sialic acid for entry to budding for releasing its progeny virus. Understanding the contribution of host factors to viral replication and immune evasion is essential for discovering new therapeutic strategies. IAV interactions with cellular proteins have been Handling Editor: Ayato Takada. * Lin Liu [email protected] 1
Oklahoma Center for Respiratory and Infectious Diseases, Oklahoma State University, Stillwater, Oklahoma, USA
Lundberg‑Kienlen Lung Biology and Toxicology Laboratory, Department of Physiological Sciences, Oklahoma State University, 264 McElroy Hall, Stillwater, OK 74078, USA
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studied intensively. Non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have now emerged as important modulators of influenza virus replication. miRNAs are a class of small RNAs with a size of 18-23 nucleotides th
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