Abstract
Viral infection of different cell types induces a unique spectrum of host defence genes, including interferon-stimulated genes (ISGs) and genes encoding other proteins with antiviral potential. Although hundreds of ISGs have been described, the vast majority have not been functionally characterised. Cellular proteins with putative antiviral activity (hereafter referred to as “restriction factors”) can target various steps in the virus life-cycle. In the context of influenza virus infection, restriction factors have been described that target virus entry, genomic replication, translation and virus release. Genome wide analyses, in combination with ectopic overexpression and/or gene silencing studies, have accelerated the identification of restriction factors that are active against influenza and other viruses, as well as providing important insights regarding mechanisms of antiviral activity. Herein, we review current knowledge regarding restriction factors that mediate anti-influenza virus activity and consider the viral countermeasures that are known to limit their impact. Moreover, we consider the strengths and limitations of experimental approaches to study restriction factors, discrepancies between in vitro and in vivo studies, and the potential to exploit restriction factors to limit disease caused by influenza and other respiratory viruses.
Highlights
Viral infection of different cell types induces a unique spectrum of host defence genes, including interferon-stimulated genes (ISGs) and genes encoding other proteins with antiviral potential
TLR3 is expressed in endosomal compartments of different cell types relevant to influenza virus infection, including Airway epithelial cells (AEC) and dendritic cells (DC)
IFITM3 may block the formation of fusion pores after virus-endosome hemifusion has occurred [33], with recent evidence implicating the importance of an amphipathic helix for IFITM3-dependent inhibition of influenza virus entry [34]
Summary
WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference. Laboratory at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia. Received: 21 November 2017; Accepted: 5 December 2017; Published: 7 December 2017
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