Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I

ABSTRACT Stimulation of the antiviral response depends on the sensing of viral pathogen-associated molecular patterns (PAMPs) by specialized cellular proteins. During infection with RNA viruses, 5′-di- or -triphosphates accompanying specific single or double-stranded RNA motifs trigger signaling of...

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Autores principales:	Jie Xu, Xiomara Mercado-López, Jennifer T. Grier, Won-keun Kim, Lauren F. Chun, Edward B. Irvine, Yoandris Del Toro Duany, Alison Kell, Sun Hur, Michael Gale, Arjun Raj, Carolina B. López
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/44e61581f5e346218856bd25e4a58991
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spelling	oai:doaj.org-article:44e61581f5e346218856bd25e4a589912021-11-15T15:41:30ZIdentification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I10.1128/mBio.01265-152150-7511https://doaj.org/article/44e61581f5e346218856bd25e4a589912015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01265-15https://doaj.org/toc/2150-7511ABSTRACT Stimulation of the antiviral response depends on the sensing of viral pathogen-associated molecular patterns (PAMPs) by specialized cellular proteins. During infection with RNA viruses, 5′-di- or -triphosphates accompanying specific single or double-stranded RNA motifs trigger signaling of intracellular RIG-I-like receptors (RLRs) and initiate the antiviral response. Although these molecular signatures are present during the replication of many viruses, it is unknown whether they are sufficient for strong activation of RLRs during infection. Immunostimulatory defective viral genomes (iDVGs) from Sendai virus (SeV) are among the most potent natural viral triggers of antiviral immunity. Here we describe an RNA motif (DVG70-114) that is essential for the potent immunostimulatory activity of 5′-triphosphate-containing SeV iDVGs. DVG70-114 enhances viral sensing by the host cell independently of the long stretches of complementary RNA flanking the iDVGs, and it retains its stimulatory potential when transferred to otherwise inert viral RNA. In vitro analysis showed that DVG70-114 augments the binding of RIG-I to viral RNA and promotes enhanced RIG-I polymerization, thereby facilitating the onset of the antiviral response. Together, our results define a new natural viral PAMP enhancer motif that promotes viral recognition by RLRs and confers potent immunostimulatory activity to viral RNA. IMPORTANCE A discrete group of molecular motifs, including 5′-triphosphates associated with double-stranded RNA, have been identified as essential for the triggering of antiviral immunity. Most RNA viruses expose these motifs during their replication; however, successful viruses normally evade immune recognition and replicate to high levels before detection, indicating that unknown factors drive antiviral immunity. DVGs from SeV are among the most potent natural viral stimuli of the antiviral response known to date. These studies define a new natural viral motif present in DVGs that maximizes viral recognition by the intracellular sensor RIG-I, allowing fast and strong antiviral responses even in the presence of viral-encoded immune antagonists. This motif can be harnessed to increase the immunostimulatory potential of otherwise inert viral RNAs and represents a novel immunostimulatory enhancer that could be used in the development of vaccine adjuvants and antivirals.Jie XuXiomara Mercado-LópezJennifer T. GrierWon-keun KimLauren F. ChunEdward B. IrvineYoandris Del Toro DuanyAlison KellSun HurMichael GaleArjun RajCarolina B. LópezAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Jie Xu Xiomara Mercado-López Jennifer T. Grier Won-keun Kim Lauren F. Chun Edward B. Irvine Yoandris Del Toro Duany Alison Kell Sun Hur Michael Gale Arjun Raj Carolina B. López Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I
description	ABSTRACT Stimulation of the antiviral response depends on the sensing of viral pathogen-associated molecular patterns (PAMPs) by specialized cellular proteins. During infection with RNA viruses, 5′-di- or -triphosphates accompanying specific single or double-stranded RNA motifs trigger signaling of intracellular RIG-I-like receptors (RLRs) and initiate the antiviral response. Although these molecular signatures are present during the replication of many viruses, it is unknown whether they are sufficient for strong activation of RLRs during infection. Immunostimulatory defective viral genomes (iDVGs) from Sendai virus (SeV) are among the most potent natural viral triggers of antiviral immunity. Here we describe an RNA motif (DVG70-114) that is essential for the potent immunostimulatory activity of 5′-triphosphate-containing SeV iDVGs. DVG70-114 enhances viral sensing by the host cell independently of the long stretches of complementary RNA flanking the iDVGs, and it retains its stimulatory potential when transferred to otherwise inert viral RNA. In vitro analysis showed that DVG70-114 augments the binding of RIG-I to viral RNA and promotes enhanced RIG-I polymerization, thereby facilitating the onset of the antiviral response. Together, our results define a new natural viral PAMP enhancer motif that promotes viral recognition by RLRs and confers potent immunostimulatory activity to viral RNA. IMPORTANCE A discrete group of molecular motifs, including 5′-triphosphates associated with double-stranded RNA, have been identified as essential for the triggering of antiviral immunity. Most RNA viruses expose these motifs during their replication; however, successful viruses normally evade immune recognition and replicate to high levels before detection, indicating that unknown factors drive antiviral immunity. DVGs from SeV are among the most potent natural viral stimuli of the antiviral response known to date. These studies define a new natural viral motif present in DVGs that maximizes viral recognition by the intracellular sensor RIG-I, allowing fast and strong antiviral responses even in the presence of viral-encoded immune antagonists. This motif can be harnessed to increase the immunostimulatory potential of otherwise inert viral RNAs and represents a novel immunostimulatory enhancer that could be used in the development of vaccine adjuvants and antivirals.
format	article
author	Jie Xu Xiomara Mercado-López Jennifer T. Grier Won-keun Kim Lauren F. Chun Edward B. Irvine Yoandris Del Toro Duany Alison Kell Sun Hur Michael Gale Arjun Raj Carolina B. López
author_facet	Jie Xu Xiomara Mercado-López Jennifer T. Grier Won-keun Kim Lauren F. Chun Edward B. Irvine Yoandris Del Toro Duany Alison Kell Sun Hur Michael Gale Arjun Raj Carolina B. López
author_sort	Jie Xu
title	Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I
title_short	Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I
title_full	Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I
title_fullStr	Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I
title_full_unstemmed	Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I
title_sort	identification of a natural viral rna motif that optimizes sensing of viral rna by rig-i
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/44e61581f5e346218856bd25e4a58991
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Identification of a Natural Viral RNA Motif That Optimizes Sensing of Viral RNA by RIG-I

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