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.IMPORTANCE 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.

• Authors: Ashish Kumar, Akhilesh Kumar, Harshad Ingle, Sushil Kumar, Richa Mishra, Mahendra Kumar Verma, Debasis Biswas, Nachimuthu Senthil Kumar, Anamika Mishra, Ashwin Ashok Raut, Akinori Takaoka, Himanshu Kumar
• Journal: Journal of virology (J Virol) Vol. 92 Issue 19 (10 01 2018) ISSN: 1098-5514 [Electronic] United States
• PMID: 30045983 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 American Society for Microbiology.

Chemical References

• Adaptor Proteins, Signal Transducing
• CUEDC2 protein, human
• Carrier Proteins
• MIRN324 microRNA, human
• Membrane Proteins
• MicroRNAs
• STAT3 Transcription Factor
• STAT3 protein, human
• Viral Proteins
• influenza virus polymerase basic protein 1
• Interferons
• JAK1 protein, human
• Janus Kinase 1
• Poly I-C

Topics

• A549 Cells
• Adaptor Proteins, Signal Transducing
• Animals
• Carrier Proteins (genetics, immunology)
• Chickens
• Gene Expression Regulation
• HEK293 Cells
• HeLa Cells
• Host-Pathogen Interactions
• Humans
• Influenza A Virus, H1N1 Subtype (genetics, immunology)
• Influenza A Virus, H5N1 Subtype (genetics, immunology)
• Influenza, Human (genetics, immunology, virology)
• Interferons (genetics, immunology)
• Janus Kinase 1 (genetics, immunology)
• Membrane Proteins (genetics, immunology)
• MicroRNAs (genetics, immunology)
• Newcastle disease virus (genetics, immunology)
• Orthomyxoviridae Infections (genetics, immunology, virology)
• Poly I-C (genetics, immunology)
• STAT3 Transcription Factor (genetics, immunology)
• Signal Transduction
• Viral Load
• Viral Proteins (genetics, immunology)
• Virus Replication