The highly pathogenic H5N1 influenza A virus down‐regulated several cellular Micro RNA s which target viral genome

• Published in: Journal of cellular and molecular medicine Vol. 21; no. 11; pp. 3076 - 3086
• Main Authors: Wang, Rong, Zhang, Ying‐Ying, Lu, Jian‐Sheng, Xia, Bing‐Hui, Yang, Zhi‐Xin, Zhu, Xu‐Dong, Zhou, Xiao‐Wei, Huang, Pei‐Tang
• Format: Journal Article
• Language: English
• Published: Chichester John Wiley & Sons, Inc 01.11.2017
• Subjects: 3' Untranslated regions; Avian flu; Genomes; Influenza A; miRNA; Pathogenesis; Replication; Transfection; Viral infections; Viruses
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13219

Abstract Higher and prolonged viral replication is critical for the increased pathogenesis of the highly pathogenic avian influenza ( HPAI ) subtype of H5N1 influenza A virus ( IAV ) over the lowly pathogenic H1N1 IAV strain. Recent studies highlighted the considerable roles of cellular mi RNA s in host defence against viral infection. In this report, using a 3′ UTR reporter system, we identified several putative mi RNA target sites buried in the H5N1 virus genome. We found two mi RNA s, miR‐584‐5p and miR‐1249, that matched with the PB 2 binding sequence. Moreover, we showed that these mi RNA s dramatically down‐regulated PB 2 expression, and inhibited replication of H5N1 and H1N1 IAV s in A549 cells. Intriguingly, these mi RNA s expression was differently regulated in A549 cells infected with the H5N1 and H1N1 viruses. Furthermore, transfection of miR‐1249 inhibitor enhanced the PB 2 expression and promoted the replication of H5N1 and H1N1 IAV s. These results suggest that H5N1 virus may have evolved a mechanism to escape host‐mediated inhibition of viral replication through down‐regulation of cellular mi RNA s, which target its viral genome.