Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling

ABSTRACT Bats are reservoirs for many RNA viruses that are highly pathogenic in humans yet relatively apathogenic in the natural host. It has been suggested that differences in innate immunity are responsible. The antiviral OAS-RNase L pathway is well characterized in humans, but there is little kno...

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Autores principales:	Yize Li, Beihua Dong, Zuzhang Wei, Robert H. Silverman, Susan R. Weiss
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	OAS-RNase L bat innate immunity Rousettus aegyptiacus Egyptian Rousette dsRNA-induced pathways OAS-RNase Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/2abfddbc4d7a4d08a4995b7c0658a0d9
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spelling	oai:doaj.org-article:2abfddbc4d7a4d08a4995b7c0658a0d92021-11-15T15:54:46ZActivation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling10.1128/mBio.02414-192150-7511https://doaj.org/article/2abfddbc4d7a4d08a4995b7c0658a0d92019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02414-19https://doaj.org/toc/2150-7511ABSTRACT Bats are reservoirs for many RNA viruses that are highly pathogenic in humans yet relatively apathogenic in the natural host. It has been suggested that differences in innate immunity are responsible. The antiviral OAS-RNase L pathway is well characterized in humans, but there is little known about its activation and antiviral activity in bats. During infection, OASs, upon sensing double-stranded RNA (dsRNA), produce 2′-5′ oligoadenylates (2-5A), leading to activation of RNase L which degrades viral and host RNA, limiting viral replication. Humans encode three active OASs (OAS1 to -3). Analysis of the Egyptian Rousette bat genome combined with mRNA sequencing from bat RoNi/7 cells revealed three homologous OAS proteins. Interferon alpha treatment or viral infection induced all three OAS mRNAs, but RNase L mRNA is constitutively expressed. Sindbis virus (SINV) or vaccinia virus (VACVΔE3L) infection of wild-type (WT) or OAS1-KO (knockout), OAS2-KO, or MAVS-KO RoNi/7 cells, but not RNase L-KO or OAS3-KO cells, induces robust RNase L activation. SINV replication is 100- to 200-fold higher in the absence of RNase L or OAS3 than in WT cells. However, MAVS-KO had no detectable effect on RNA degradation or replication. Thus, in RoNi/7 bat cells, as in human cells, activation of RNase L during infection and its antiviral activity are dependent primarily on OAS3 while MAVS signaling is not required for the activation of RNase L and restriction of infection. Our findings indicate that OAS proteins serve as pattern recognition receptors (PRRs) to recognize viral dsRNA and that this pathway is a primary response to virus rather than a secondary effect of interferon signaling. IMPORTANCE Many RNA viruses that are highly pathogenic in humans are relatively apathogenic in their bat reservoirs, making it important to compare innate immune responses in bats to those well characterized in humans. One such antiviral response is the OAS-RNase L pathway. OASs, upon sensing dsRNA, produce 2-5A, leading to activation of RNase L which degrades viral and host RNA, limiting viral replication. Analysis of Egyptian Rousette bat sequences revealed three OAS genes expressing OAS1, OAS2, and OAS3 proteins. Interferon treatment or viral infection induces all three bat OAS mRNAs. In these bat cells as in human cells, RNase L activation and its antiviral activity are dependent primarily on OAS3 while MAVS signaling is not required. Importantly, our findings indicate the OAS-RNase L system is a primary response to virus rather than a secondary effect of interferon signaling and therefore can be activated early in infection or while interferon signaling is antagonized.Yize LiBeihua DongZuzhang WeiRobert H. SilvermanSusan R. WeissAmerican Society for MicrobiologyarticleOAS-RNase Lbat innate immunityRousettus aegyptiacusEgyptian RousettedsRNA-induced pathwaysOAS-RNaseMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	OAS-RNase L bat innate immunity Rousettus aegyptiacus Egyptian Rousette dsRNA-induced pathways OAS-RNase Microbiology QR1-502
spellingShingle	OAS-RNase L bat innate immunity Rousettus aegyptiacus Egyptian Rousette dsRNA-induced pathways OAS-RNase Microbiology QR1-502 Yize Li Beihua Dong Zuzhang Wei Robert H. Silverman Susan R. Weiss Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling
description	ABSTRACT Bats are reservoirs for many RNA viruses that are highly pathogenic in humans yet relatively apathogenic in the natural host. It has been suggested that differences in innate immunity are responsible. The antiviral OAS-RNase L pathway is well characterized in humans, but there is little known about its activation and antiviral activity in bats. During infection, OASs, upon sensing double-stranded RNA (dsRNA), produce 2′-5′ oligoadenylates (2-5A), leading to activation of RNase L which degrades viral and host RNA, limiting viral replication. Humans encode three active OASs (OAS1 to -3). Analysis of the Egyptian Rousette bat genome combined with mRNA sequencing from bat RoNi/7 cells revealed three homologous OAS proteins. Interferon alpha treatment or viral infection induced all three OAS mRNAs, but RNase L mRNA is constitutively expressed. Sindbis virus (SINV) or vaccinia virus (VACVΔE3L) infection of wild-type (WT) or OAS1-KO (knockout), OAS2-KO, or MAVS-KO RoNi/7 cells, but not RNase L-KO or OAS3-KO cells, induces robust RNase L activation. SINV replication is 100- to 200-fold higher in the absence of RNase L or OAS3 than in WT cells. However, MAVS-KO had no detectable effect on RNA degradation or replication. Thus, in RoNi/7 bat cells, as in human cells, activation of RNase L during infection and its antiviral activity are dependent primarily on OAS3 while MAVS signaling is not required for the activation of RNase L and restriction of infection. Our findings indicate that OAS proteins serve as pattern recognition receptors (PRRs) to recognize viral dsRNA and that this pathway is a primary response to virus rather than a secondary effect of interferon signaling. IMPORTANCE Many RNA viruses that are highly pathogenic in humans are relatively apathogenic in their bat reservoirs, making it important to compare innate immune responses in bats to those well characterized in humans. One such antiviral response is the OAS-RNase L pathway. OASs, upon sensing dsRNA, produce 2-5A, leading to activation of RNase L which degrades viral and host RNA, limiting viral replication. Analysis of Egyptian Rousette bat sequences revealed three OAS genes expressing OAS1, OAS2, and OAS3 proteins. Interferon treatment or viral infection induces all three bat OAS mRNAs. In these bat cells as in human cells, RNase L activation and its antiviral activity are dependent primarily on OAS3 while MAVS signaling is not required. Importantly, our findings indicate the OAS-RNase L system is a primary response to virus rather than a secondary effect of interferon signaling and therefore can be activated early in infection or while interferon signaling is antagonized.
format	article
author	Yize Li Beihua Dong Zuzhang Wei Robert H. Silverman Susan R. Weiss
author_facet	Yize Li Beihua Dong Zuzhang Wei Robert H. Silverman Susan R. Weiss
author_sort	Yize Li
title	Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling
title_short	Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling
title_full	Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling
title_fullStr	Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling
title_full_unstemmed	Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling
title_sort	activation of rnase l in egyptian rousette bat-derived roni/7 cells is dependent primarily on oas3 and independent of mavs signaling
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/2abfddbc4d7a4d08a4995b7c0658a0d9
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Activation of RNase L in Egyptian Rousette Bat-Derived RoNi/7 Cells Is Dependent Primarily on OAS3 and Independent of MAVS Signaling

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