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

• Published in: Journal of cellular and molecular medicine 2017-11, Vol.21 (11), p.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: Article
• Language: English
• Subjects: 3' Untranslated Regions; A549 Cells; Animals; Antagomirs - genetics; Antagomirs - metabolism; Base Sequence; Binding Sites; Dogs; Gene Expression Regulation; Genes, Reporter; Genome, Viral; H1N1; H5N1 HPAI; HEK293 Cells; host defence; Host-Pathogen Interactions; Humans; Influenza A Virus, H1N1 Subtype - genetics; Influenza A Virus, H1N1 Subtype - metabolism; Influenza A Virus, H5N1 Subtype - genetics; Influenza A Virus, H5N1 Subtype - metabolism; Luciferases - genetics; Luciferases - metabolism; Madin Darby Canine Kidney Cells; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Original; Protein Binding; RNA Replicase - genetics; RNA Replicase - metabolism; Signal Transduction; Viral Proteins - genetics; Viral Proteins - metabolism; virus replication; Virus Replication - genetics
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13219

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 miRNAs in host defence against viral infection. In this report, using a 3′UTR reporter system, we identified several putative miRNA target sites buried in the H5N1 virus genome. We found two miRNAs, miR‐584‐5p and miR‐1249, that matched with the PB2 binding sequence. Moreover, we showed that these miRNAs dramatically down‐regulated PB2 expression, and inhibited replication of H5N1 and H1N1 IAVs in A549 cells. Intriguingly, these miRNAs expression was differently regulated in A549 cells infected with the H5N1 and H1N1 viruses. Furthermore, transfection of miR‐1249 inhibitor enhanced the PB2 expression and promoted the replication of H5N1 and H1N1 IAVs. These results suggest that H5N1 virus may have evolved a mechanism to escape host‐mediated inhibition of viral replication through down‐regulation of cellular miRNAs, which target its viral genome.