Temporal- and Strain-Specific Host MicroRNA Molecular Signatures Associated with Swine-Origin H1N1 and Avian-Origin H7N7 Influenza A Virus Infection

Loveday, Emma-Kate; Svinti, Victoria; Diederich, Sandra; Pasick, John; Jean, François

doi:10.1128/jvi.06892-11

Cited by 85 publications

(101 citation statements)

References 64 publications

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“…In addition, temporal-and strain-specific miRNA expression was profiled in A549 cells infected with either pandemic H1N1 (2009) or H7N7 (2003), but these studies lacked the pressure normally exerted by the host immune system (28). Consequently, longitudinal changes in miRNA expression and their targets during influenza infection and how they relate to viral replication and host response in vivo remain poorly understood.…”

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confidence: 99%

microRNAs Regulate Host Immune Response and Pathogenesis During Influenza Infection in Rhesus Macaques

et al. 2016

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microRNAs (miRNAs) are small noncoding RNAs that are key regulators of biological processes, including the immune response to viral infections. Differential expression levels of cellular miRNAs and their predicted targets have been described in the lungs of H1N1-infected BALB/c mice, the lungs of H5N1 influenza-infected cynomolgus macaques, and in peripheral blood mononuclear cells (PBMCs) of critically ill patients infected with 2009 pandemic H1N1. However, a longitudinal analysis of changes in the expression of miRNAs and their targets during influenza infection and how they relate to viral replication and host response has yet to be carried out. In the present study, we conducted a comprehensive analysis of innate and adaptive immune responses as well as the expression of several miRNAs and their validated targets in both peripheral blood and bronchoalveolar lavage (BAL) collected from rhesus macaques over the course of infection with the 2009 H1N1 virus A/Mexico/4108/2009 (MEX4108). We describe a distinct set of differentially expressed miRNAs in BAL and PBMCs, which regulate the expression of genes involved in inflammation, immune response, and regulation of cell cycle and apoptosis.

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confidence: 99%

microRNAs Regulate Host Immune Response and Pathogenesis During Influenza Infection in Rhesus Macaques

et al. 2016

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“…Influenza A virus infection involves many host factors including miRNAs Loveday et al, 2012). It has been reported that influenza A virus infection causes changes in the profile of host miRNAs.…”

Section: Identification Of Mirnas Suppressing Influenza a Virus Replimentioning

confidence: 99%

MicroRNA-33a disturbs influenza A virus replication by targeting ARCN1 and inhibiting viral ribonucleoprotein activity

Jiang

Lai

et al. 2016

Journal of General Virology

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In order to explore the roles of microRNA(s) [miRNA(s)] in the influenza A virus life cycle, we compared the miRNA profiles of 293T and HeLa cell lines, as influenza A virus can replicate efficiently in 293T cells but only poorly in HeLa cells. We analysed differentially expressed miRNAs and identified five, including miR-33a, that could disturb influenza A virus replication significantly. Using TargetScan analysis, we found that ARCN1 could be a potential target of miR-33a. To confirm whether miR-33a could truly target ARCN1, we generated a luciferase reporter for the ARCN1 39 untranslated region (UTR) and performed a luciferase assay. The data indicated that miR-33a could suppress the luciferase activity of the reporter for the ARCN1 39 UTR but not a reporter in which the predicted miR-33a targeting sites on ARCN1 39 UTR were mutated. We performed immunoblotting to confirm that miR-33a could downregulate the protein level of ARCN1. Consistently, the level of ARCN1 protein in HeLa cells was significantly lower than that in 293T cells. We also demonstrated that ectopic expression of ARCN1 could partially rescue the inhibitory effect of miR-33a on virus replication. Furthermore, we demonstrated that miR-33a could impede virus replication at the stage of virus internalization, which was similar to the pattern for knockdown of ARCN1, indicating that miR-33a inhibits influenza virus infection by suppressing ARCN1 expression. In addition, we found that miR-33a could also weaken the viral ribonucleoprotein activity in an ARCN1-independent manner. In conclusion, we found that miR-33a is a novel inhibitory factor for influenza A virus replication.

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“…Microarray analysis of mouse miRNA expression during infection with the reconstructed 1918 pandemic influenza virus and a seasonal H1N1 virus (Tx/91) established that the miRNAome was modulated during infA infection (Li et al, 2010). In our previous study, we profiled human miRNA expression during infection with the low-pathogenicity (LP) swine-origin 2009 pandemic H1N1 infA and the highly pathogenic (HP) avian-origin H7N7 infA (Loveday et al, 2012). Our studies demonstrated temporal and strain-specific regulation of miRNAs during infA infection, especially for the HP H7N7 virus.…”

Section: Introductionmentioning

confidence: 99%

Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin

Loveday

Diederich

Pasick

et al. 2015

Journal of General Virology

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A common critical cellular event that many human enveloped viruses share is the requirement for proteolytic cleavage of the viral glycoprotein by furin in the host secretory pathway. For example, the furin-dependent proteolytic activation of highly pathogenic (HP) influenza A (infA) H5 and H7 haemagglutinin precursor (HA0) subtypes is critical for yielding fusion-competent infectious virions. In this study, we hypothesized that viral hijacking of the furin pathway by HP infA viruses to permit cleavage of HA0 could represent a novel molecular mechanism controlling the dynamic production of fusion-competent infectious virus particles during the viral life cycle. We explored the biological role of a newly identified furin-directed human microRNA, miR-24, in this process as a potential post-transcriptional regulator of the furin-mediated activation of HA0 and production of fusion-competent virions in the host secretory pathway. We report that miR-24 and furin are differentially expressed in human A549 cells infected with HP avian-origin infA H5N1. Using miR-24 mimics, we demonstrated a robust decrease in both furin mRNA levels and intracellular furin activity in A549 cells. Importantly, pretreatment of A549 cells with miR-24 mimicked these results: a robust decrease of H5N1 infectious virions and a complete block of H5N1 virus spread that was not observed in A549 cells infected with low-pathogenicity swine-origin infA H1N1 virus. Our results suggest that viral-specific downregulation of furin-directed microRNAs such as miR-24 during the life cycle of HP infA viruses may represent a novel regulatory mechanism that governs furin-mediated proteolytic activation of HA0 glycoproteins and production of infectious virions.

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Temporal- and Strain-Specific Host MicroRNA Molecular Signatures Associated with Swine-Origin H1N1 and Avian-Origin H7N7 Influenza A Virus Infection

Cited by 85 publications

References 64 publications

microRNAs Regulate Host Immune Response and Pathogenesis During Influenza Infection in Rhesus Macaques

microRNAs Regulate Host Immune Response and Pathogenesis During Influenza Infection in Rhesus Macaques

MicroRNA-33a disturbs influenza A virus replication by targeting ARCN1 and inhibiting viral ribonucleoprotein activity

Human microRNA-24 modulates highly pathogenic avian-origin H5N1 influenza A virus infection in A549 cells by targeting secretory pathway furin

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