Viruses, endoplasmic reticulum stress, and interferon responses.
Viral infection induces endoplasmic reticulum (ER) stress and interferon responses. While viral double-stranded RNA intermediates trigger interferon responses, viral polypeptides synthesized during infection stimulate ER stress. Among the interferon-regulated gene products, the double-stranded RNA-dependent protein kinase (PKR) plays a key role in limiting viral replication. Thus, to establish productive infection, viruses have evolved mechanisms to overcome the deleterious effects of PKR. It has become clear that ER stress causes translational attenuation and transcriptional upregulation of genes encoding proteins that facilitate folding or degradation of proteins. Notably, prolonged ER stress triggers apoptosis. Therefore, viruses are confronted with the consequences of ER stress. Emerging evidence suggests that viruses not only interfere with the interferon system involving PKR but also manipulate the programs emanating from the ER in a complex way, which may facilitate viral replication or pathogenesis. This review highlights recent progress in these areas.
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Department of Microbiology and Immunology, College of Medicine, The University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, IL 60612, USA. tshuo@uic.edu
D051702:Activating Transcription Factor 6 / Q000378:metabolism; D017209:Apoptosis; D004721:Endoplasmic Reticulum / Q000502:physiology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007372:Interferons / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014777:Virus Diseases / Q000378:metabolism / Q000821:virology*; D014779:Virus Replication; D014780:Viruses / Q000472:pathogenicity*; D019892:eIF-2 Kinase / Q000378:metabolism
D051702:Activating Transcription Factor 6; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase