title: Innate immune restriction and antagonism of viral RNA lacking 2׳-O methylation.
abstract: N-7 and 2'-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m(7)GpppN; cap 1, m(7)GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2'-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2'-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5'-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.
authors: Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110, USA.
authors: Jennifer L
authors: JL
authors: Hyde
authors: Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110, USA; Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110 USA; Pathology & Immunology, Washington University School of Medicine, St Louis., MO 63110, USA; The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis., MO 63110, USA. Electronic address: diamond@borcim.wustl.edu.
authors: Michael S
authors: MS
authors: Diamond
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000378:metabolism; D054884:Host-Pathogen Interactions; D057131:Immune Evasion; D009690:Nucleic Acid Conformation; D012315:RNA Caps; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism*; D016601:RNA-Binding Proteins; D014780:Viruses / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C484290:IFIT1 protein, human; D012315:RNA Caps; D012333:RNA, Messenger; D012367:RNA, Viral; D016601:RNA-Binding Proteins
keywords: Immune evasion; Innate immunity; Interferon; Methylation; RNA structure; Viral pathogenesis