Open AccessmiR-29a is a negative regulator of influenza virus infection through targeting of the frizzled 5 receptor
Author(s) -
Xiaoyun Yang,
Yurong Liang,
Gayan Bamunuarachchi,
Yong Xu,
Kishore Vaddadi,
Samuel Pushparaj,
Dao Xu,
Zhengyu Zhu,
R. Bláha,
Chaoqun Huang,
Lin Liu
Publication year - 2020
Publication title -
archives of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.943
H-Index - 110
eISSN - 1432-8798
pISSN - 0304-8608
DOI - 10.1007/s00705-020-04877-z
Subject(s) - biology , hek 293 cells , influenza a virus , virology , frizzled , virus , wnt signaling pathway , untranslated region , three prime untranslated region , messenger rna , receptor , immunology , signal transduction , gene , microbiology and biotechnology , genetics
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-Ca 2+ 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.