Abstract

During infection, viruses enter susceptible host cells in order to replicate their components for production of new virions. In the process of infection, the gene expression of infected cells undergoes changes because of the production of viral components and due to the host response from detection of viral products. In the advent of RNA sequencing, the discovery of new genes and their functions in the host response generates new avenues for interventions in the host-pathogen interaction. We have identified a novel gene, Heatr9, as a virus and cytokine inducible viral responsive gene. We confirm Heatr9’s expression in vitro and in vivo during virus infection and correlate it with viral burden. Heatr9 is induced by influenza virus and RSV. Heatr9 knockdown during viral infection was shown to affect chemokine expression. Our studies identify Heatr9 as a novel inflammatory and virus infection induced gene that can regulate the induction of specific cytokines.

Highlights

  • One of the most well studied models of an acute immune response to an infectious pathogen, there are still many areas which remain to be elucidated in influenza virus infection

  • HEAT repeat containing protein 9 (Heatr9) was found to be induced by influenza virus infection plateaued at day six where its expression remained constant until day ten (Fig 1A)

  • An in vitro model of influenza virus infection was utilized with A549 cells, a human lung epithelial cell line, effectively removing the effect of any infiltrating immune cells or cytokines produced by these cells

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Summary

Introduction

One of the most well studied models of an acute immune response to an infectious pathogen, there are still many areas which remain to be elucidated in influenza virus infection. In the advent of new, more affordable technologies, like whole transcriptome RNA Sequencing [1, 2], RNA interference screens [3], CRISPR/Cas screenings [4, 5], global methylation profiling [6], Chromatin Immunoprecipitation (ChIP) assay [7, 8], and others, more knowledge is constantly being acquired as to what constitutes the host immune response to influenza virus infection These new strategies instruct us as to what changes occur during infection and allow the potential elucidation of the functional effects of these changes during viral infection.

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