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Arch Virol . miR-29a is a negative regulator of influenza virus infection through targeting of the frizzled 5 receptor

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  • Arch Virol . miR-29a is a negative regulator of influenza virus infection through targeting of the frizzled 5 receptor


    Arch Virol


    . 2020 Nov 18.
    doi: 10.1007/s00705-020-04877-z. Online ahead of print.
    miR-29a is a negative regulator of influenza virus infection through targeting of the frizzled 5 receptor


    Xiaoyun Yang 1 2 , Yurong Liang 1 2 , Gayan Bamunuarachchi 1 2 , Yanzhao Xu 1 2 , Kishore Vaddadi 1 2 , Samuel Pushparaj 1 2 , Dao Xu 1 2 , Zhengyu Zhu 1 2 , Rachel Blaha 2 , Chaoqun Huang 1 2 , Lin Liu 3 4



    Affiliations

    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.


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