MicroRNA hsa-miR-324-5p Suppresses H5N1 Virus Replication by Targeting the Viral PB1 and Host CUEDC2

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that are crucial posttranscriptional regulators for host mRNAs. Recent studies indicate that miRNAs may modulate host response during RNA virus infection. However, the role of miRNAs in immune response against H5N1 infection is not clearly understood. In this study, we showed that expression of cellular miRNA miR-324-5p was downregulated in A549 cells in response to infection with RNA viruses H5N1, A/PR8/H1N1, and Newcastle disease virus (NDV) and transfection with poly(I·C). We found that miR-324-5p inhibited H5N1 replication by targeting the PB1 viral RNA of H5N1 in host cells. In addition, transcriptome analysis revealed that miR-324-5p enhanced the expression of type I interferon, type III interferon, and interferon-inducible genes (ISGs) by targeting CUEDC2, the negative regulator of the JAK1-STAT3 pathway. Together, these findings highlight that the miR-324-5p plays a crucial role in host defense against H5N1 by targeting viral PB1 and host CUEDC2 to inhibit H5N1 replication. Highly pathogenic influenza A virus (HPAIV) continues to pose a pandemic threat globally. From 2003 to 2017, H5N1 HPAIV caused 453 human deaths, giving it a high mortality rate (52.74%). This work shows that miR-324-5p suppresses H5N1 HPAIV replication by directly targeting the viral genome (thereby inhibiting viral gene expression) and cellular CUEDC2 gene, the negative regulator of the interferon pathway (thereby enhancing antiviral genes). Our study enhances the knowledge of the role of microRNAs in the cellular response to viral infection. Also, the study provides help in understanding how the host cells utilize small RNAs in controlling the viral burden.

Particulate matter (PM10) enhances RNA virus infection through modulation of innate immune responses

“…Airborne PM 10 treated A549 cells were infected with New-castle Disease Virus (NDV) – LaSota strain, Highly Pathogenic Avian Influenza virus (H5N1) - A/duck/India/02CA10/2011 strain and vaccine strain PR8 virus (H1N1) – A/PR8/H1N1 virus was generated using the eight plasmid reverse genetics system ( Kumar et al., 2018 ), at respective multiplicity of infection as mentioned in the figures and/or figure legends. PM 10 treated A549 cells were washed by 1X PBS (phosphate-buffered saline) solution and infected with appropriate RNA viruses in serum-free media as per the subsequent experiment then after 60 min, virus containing media was removed from the cells and cells were washed once with 1X PBS solution.…”

Integrated Analysis of microRNA-mRNA Expression in Mouse Lungs Infected With H7N9 Influenza Virus: A Direct Comparison of Host-Adapting PB2 Mutants

“…For example, miR-466i-3p down-regulated the expression of Agap3, Bcl2l11, Vegfa, Arf3, Gsk3b, Psd3, Mylk, Kit, Nedd4l, Efnb2, and Ephb3, while Akt3 could be up-regulated by miR-320-3p, miR-181d-5p, and miR-425-5p, indicating that these miRNA-mRNA networks were complicated and ordered. Previous studies showed that TGF-β signaling pathway (Schultz-Cherry and Hinshaw, 1996;Jones et al, 2005) and JAK-STAT signaling pathway (Kumar et al, 2018) participate in the processes of cell cycle control, differentiation, apoptosis, and innate immunity. Our pathway enrichment analysis results also identified the same pathways, indicating that some of the differentially expressed miRNAs induced by the three PB2-variant viruses may affect the pathophysiological process of influenza virus infection.…”

The miRNA-gene regulatory circuits in nSARS-CoV-2 and their potential correlations with pulmonary and thrombotic disorders

“…Hence hsa-miR-9-5p can be used as a potential target to regulate endocytosis of nSARS-CoV-2 viral RNA and uncontrolled lung inflammation. In FFL A: hsa-miR-9-5p is found to regulats E1A Binding Protein P300 (EP300), a known transcriptional co-activator protein of Hypoxia-Inducible Factor-1(HIF-1) [47]. In FFL B, hsa-miR-324-3p deregulates MYC which is a known transcription factor and oncogene controlling cell cycle progression, cell proliferation, and apoptosis [48].…”