Sus scrofa miR-204 and miR-4331 Negatively Regulate Swine H1N1/2009 Influenza A Virus Replication by Targeting Viral HA and NS, Respectively

Abstract

The prevalence of swine pandemic H1N1/2009 influenza A virus (SIV-H1N1/2009) in pigs has the potential to generate novel reassortant viruses, posing a great threat to human health. Cellular microRNAs (miRNAs) have been proven as promising small molecules for regulating influenza A virus replication by directly targeting viral genomic RNA. In this study, we predicted potential Sus scrofa (ssc-, swine) miRNAs targeting the genomic RNA of SIV-H1N1/2009 by RegRNA 2.0, and identified ssc-miR-204 and ssc-miR-4331 to target viral HA and NS respectively through dual-luciferase reporter assays. The messenger RNA (mRNA) levels of viral HA and NS were significantly suppressed when newborn pig trachea (NPTr) cells respectively overexpressed ssc-miR-204 and ssc-miR-4331 and were infected with SIV-H1N1/2009, whereas the suppression effect could be restored when respectively decreasing endogenous ssc-miR-204 and ssc-miR-4331 with inhibitors. Because of the importance of viral HA and NS in the life cycle of influenza A virus, ssc-miR-204 and ssc-miR-4331 exhibited an inhibition effect on SIV-H1N1/2009 replication. The antiviral effect was sequence-specific of SIV-H1N1/2009, for the target sites in HA and NS of H5N1 or H9N2 influenza A virus were not conserved. Furthermore, SIV-H1N1/2009 infection reversely downregulated the expression of ssc-miR-204 and ssc-miR-4331, which might facilitate the virus replication in the host. In summary, this work will provide us some important clues for controlling the prevalence of SIV-H1N1/2009 in pig populations.

Synchronized Orchestration of miR-99b and let-7g Positively Regulates Rotavirus Infection by Modulating Autophagy

“…Emerging evidence suggests that cellular miRNAs play a vital role in the regulation of viral replication 39 . miR-204 and miR-4331 inhibit influenza A virus replication by targeting viral HA and NS gene, respectively 23 . miR-181c limits HCV replication by targeting HOXA1 as well as viral genome 12 .…”

“…Emerging line of evidence suggests that miRNAs are closely linked to virtually all known fundamental biological pathways like stress response, proliferation, differentiation, apoptosis, autophagy etc 8,19,20 . Cooperative interactions between multiple microRNAs regulating multiple targets result in an additive effect on many important biological processes 21–23 . Autophagy is a tightly regulated catabolic process, which plays an essential role in maintaining cellular homeostasis and restriction of pathogen replication 24 .…”

MicroRNA 876-5p modulates EV-A71 replication through downregulation of host antiviral factors

“…In deed, the regulation of miRNAs with specific genes in cells can modulate specific biological pathways. The extensive dysregulation of miRNA expression may reflect multiple cellular defense responses caused by inflammation, bacterial infections, and viral infections [34][35][36]. Upon viral infection, the host can alter several specific biological pathways, such as differentiated growth, development, apoptosis, changes in metabolic pathway, and homeostasis.…”

Molecular Research on Emerging Viruses: Evolution, Diagnostics, Pathogenesis, and Therapeutics

“…In the article by Eng et al, a machine learning approach was taken to build a zoonotic strain prediction model which could classify avian, human, or zoonotic strains with an estimated zoonotic risk [ 9 ]. In another article, Zhang et al investigated the role of swine cellular microRNAs in regulating swine pandemic H1N1/2009 influenza A virus (SIV-H1N1/2009) replication [ 10 ]. Two microRNAs, ssc-miR-204 and ssc-miR-4431, were found to target viral haemagglutinin (HA) and non-structural protein (NS), respectively, and inhibit viral replication, providing insights into virus–host interaction and control of the virus in swine population.…”