RIG-I Detects Kaposi’s Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner

ABSTRACT Retinoic acid-inducible gene I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the innate immune response against many RNA viruses. We previously showed that RIG-I restricts Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation (J. A. West et al., J Virol 88:5...

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Autores principales:	Yugen Zhang, Dirk P. Dittmer, Piotr A. Mieczkowski, Kurtis M. Host, William G. Fusco, Joseph A. Duncan, Blossom Damania
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Kaposi's sarcoma-associated herpesvirus RIG-I innate immunity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ea1202ece30e43b08006e1d2fdd3d1e8
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spelling	oai:doaj.org-article:ea1202ece30e43b08006e1d2fdd3d1e82021-11-15T16:00:15ZRIG-I Detects Kaposi’s Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner10.1128/mBio.00823-182150-7511https://doaj.org/article/ea1202ece30e43b08006e1d2fdd3d1e82018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00823-18https://doaj.org/toc/2150-7511ABSTRACT Retinoic acid-inducible gene I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the innate immune response against many RNA viruses. We previously showed that RIG-I restricts Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation (J. A. West et al., J Virol 88:5778–5787, 2014, https://doi.org/10.1128/JVI.03226-13). In this study, we report that KSHV stimulates the RIG-I signaling pathway in a RNA polymerase (Pol) III-independent manner and subsequently induces type I interferon (IFN) responses. Knockdown or inhibition of RNA Pol III had no effect on beta interferon (IFN-β) induction by KSHV. By using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) approach, we identified multiple KSHV regions that give rise to RNA fragments binding to RIG-I, such as ORF810420-10496, Repeat region (LIR1)119059-119204, and ORF2543561-43650. The sequence dissimilarity between these fragments suggests that RIG-I detects a particular structure rather than a specific sequence motif. Synthesized ORF810420-10496 RNA stimulated RIG-I-dependent but RNA Pol III-independent IFN-β signaling. In summary, several KSHV RNAs are sensed by RIG-I in a RNA Pol III-independent manner. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. Innate immune responses against viral infections, especially the induction of type I interferon, are critical for limiting the replication of viruses. Retinoic acid-inducible gene I (RIG-I), a cytosolic RNA helicase sensor, plays a significant role in the induction of type I interferon responses following viral infection. Here, we identified multiple RNA regions in KSHV as potential virus ligands that bind to RIG-I and stimulate RIG-I-dependent but RNA Pol III-independent IFN-β signaling. Our results expand the role of RIG-I by providing an example of a DNA virus activating a canonical RNA-sensing pathway.Yugen ZhangDirk P. DittmerPiotr A. MieczkowskiKurtis M. HostWilliam G. FuscoJoseph A. DuncanBlossom DamaniaAmerican Society for MicrobiologyarticleKaposi's sarcoma-associated herpesvirusRIG-Iinnate immunityMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Kaposi's sarcoma-associated herpesvirus RIG-I innate immunity Microbiology QR1-502
spellingShingle	Kaposi's sarcoma-associated herpesvirus RIG-I innate immunity Microbiology QR1-502 Yugen Zhang Dirk P. Dittmer Piotr A. Mieczkowski Kurtis M. Host William G. Fusco Joseph A. Duncan Blossom Damania RIG-I Detects Kaposi’s Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner
description	ABSTRACT Retinoic acid-inducible gene I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the innate immune response against many RNA viruses. We previously showed that RIG-I restricts Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation (J. A. West et al., J Virol 88:5778–5787, 2014, https://doi.org/10.1128/JVI.03226-13). In this study, we report that KSHV stimulates the RIG-I signaling pathway in a RNA polymerase (Pol) III-independent manner and subsequently induces type I interferon (IFN) responses. Knockdown or inhibition of RNA Pol III had no effect on beta interferon (IFN-β) induction by KSHV. By using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) approach, we identified multiple KSHV regions that give rise to RNA fragments binding to RIG-I, such as ORF810420-10496, Repeat region (LIR1)119059-119204, and ORF2543561-43650. The sequence dissimilarity between these fragments suggests that RIG-I detects a particular structure rather than a specific sequence motif. Synthesized ORF810420-10496 RNA stimulated RIG-I-dependent but RNA Pol III-independent IFN-β signaling. In summary, several KSHV RNAs are sensed by RIG-I in a RNA Pol III-independent manner. IMPORTANCE Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. Innate immune responses against viral infections, especially the induction of type I interferon, are critical for limiting the replication of viruses. Retinoic acid-inducible gene I (RIG-I), a cytosolic RNA helicase sensor, plays a significant role in the induction of type I interferon responses following viral infection. Here, we identified multiple RNA regions in KSHV as potential virus ligands that bind to RIG-I and stimulate RIG-I-dependent but RNA Pol III-independent IFN-β signaling. Our results expand the role of RIG-I by providing an example of a DNA virus activating a canonical RNA-sensing pathway.
format	article
author	Yugen Zhang Dirk P. Dittmer Piotr A. Mieczkowski Kurtis M. Host William G. Fusco Joseph A. Duncan Blossom Damania
author_facet	Yugen Zhang Dirk P. Dittmer Piotr A. Mieczkowski Kurtis M. Host William G. Fusco Joseph A. Duncan Blossom Damania
author_sort	Yugen Zhang
title	RIG-I Detects Kaposi’s Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner
title_short	RIG-I Detects Kaposi’s Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner
title_full	RIG-I Detects Kaposi’s Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner
title_fullStr	RIG-I Detects Kaposi’s Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner
title_full_unstemmed	RIG-I Detects Kaposi’s Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner
title_sort	rig-i detects kaposi’s sarcoma-associated herpesvirus transcripts in a rna polymerase iii-independent manner
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/ea1202ece30e43b08006e1d2fdd3d1e8
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RIG-I Detects Kaposi’s Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner

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