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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{sup 7}GpppN; cap 1, m{sup 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:
 [1];  [1];  [2];  [2];  [2]
  1. Departments of Medicine, Washington University School of Medicine, St Louis., MO 63110 (United States)
  2. (United States)
Publication Date:
OSTI Identifier:
22470164
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 479-480; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CYTOPLASM; DISEASES; GENES; IMMUNITY; INTERFERON; MESSENGER-RNA; METHYL TRANSFERASES; METHYLATION; MODIFICATIONS; PATHOGENS; REVIEWS; SPLICING; SYNTHESIS; VIRUSES

Citation Formats

Hyde, Jennifer L., Diamond, Michael S., E-mail: diamond@borcim.wustl.edu, Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110, Pathology & Immunology, Washington University School of Medicine, St Louis., MO 63110, and The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis., MO 63110. Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation. United States: N. p., 2015. Web. doi:10.1016/J.VIROL.2015.01.019.
Hyde, Jennifer L., Diamond, Michael S., E-mail: diamond@borcim.wustl.edu, Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110, Pathology & Immunology, Washington University School of Medicine, St Louis., MO 63110, & The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis., MO 63110. Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation. United States. doi:10.1016/J.VIROL.2015.01.019.
Hyde, Jennifer L., Diamond, Michael S., E-mail: diamond@borcim.wustl.edu, Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110, Pathology & Immunology, Washington University School of Medicine, St Louis., MO 63110, and The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis., MO 63110. Fri . "Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation". United States. doi:10.1016/J.VIROL.2015.01.019.
@article{osti_22470164,
title = {Innate immune restriction and antagonism of viral RNA lacking 2'-O methylation},
author = {Hyde, Jennifer L. and Diamond, Michael S., E-mail: diamond@borcim.wustl.edu and Molecular Microbiology, Washington University School of Medicine, St Louis., MO 63110 and Pathology & Immunology, Washington University School of Medicine, St Louis., MO 63110 and The Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St Louis., MO 63110},
abstractNote = {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{sup 7}GpppN; cap 1, m{sup 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.},
doi = {10.1016/J.VIROL.2015.01.019},
journal = {Virology},
issn = {0042-6822},
number = ,
volume = 479-480,
place = {United States},
year = {2015},
month = {5}
}