Influenza A Virus Infection of Human Respiratory Cells Induces Primary MicroRNA Expression*

William A. Buggele , Karen E. Johnson, and Curt M. Horvath

The cellular response to virus infection is initiated by recognition of the invading pathogen and subsequent changes in gene expression mediated by both transcriptional and translational mechanisms. In addition to well established means of regulating antiviral gene expression, it has been demonstrated that RNA interference (RNAi) can play an important role in antiviral responses. Virus-derived small interfering RNA (siRNA) is a primary antiviral response exploited by plants and invertebrate animals, and host-encoded microRNA (miRNA) species have been clearly implicated in the regulation of innate and adaptive immune responses in mammals and other vertebrates. Examination of miRNA abundance in human lung cell lines revealed endogenous miRNAs, including miR-7, miR-132, miR-146a, miR-187, miR-200c, and miR-1275, to specifically accumulate in response to infection with two influenza A virus strains, A/Udorn/72 and A/WSN/33. Known antiviral response pathways, including Toll like receptor, RIG-I-like receptor, and direct interferon or cytokine stimulation did not alter the abundance of the tested miRNAs to the extent of influenza A virus infection, which initiates primary miRNA transcription via a secondary response pathway. Gene expression profiling identified 26 cellular mRNAs targeted by these miRNAs, including IRAK1, MAPK3, and other components of innate immune signaling systems.


EpiAirway (AIR-100), innate immunity, Influenza A virus, MicroRNAs, mRNA, viral infection, signal transduction, miR-7, miR-16, miR-21, miR-132, miR-146a, miR-187, miR-200c, miR-1275, CCL5, IL-28a, IFN-b, ISG15, influenza A/Udorn/72 strain, influenza A/WSN/33 strain, influenza nucleoprotein

Materials Tested

influenza A/Udorn/72 strain, influenza A/WSN/33 strain

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