Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells

ABSTRACT Small RNAs play a critical role in host-pathogen interaction. Indeed, small RNA-mediated silencing or RNA interference (RNAi) is one of the earliest forms of antiviral immunity. Although it represents the main defense system against viruses in many organisms, the antiviral role of RNAi has...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Erika Girardi, Béatrice Chane-Woon-Ming, Mélanie Messmer, Pasi Kaukinen, Sébastien Pfeffer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e6b1ce8553864c5da1f666e2f8bf580b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e6b1ce8553864c5da1f666e2f8bf580b
record_format	dspace
spelling	oai:doaj.org-article:e6b1ce8553864c5da1f666e2f8bf580b2021-11-15T15:42:31ZIdentification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells10.1128/mBio.00698-132150-7511https://doaj.org/article/e6b1ce8553864c5da1f666e2f8bf580b2013-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00698-13https://doaj.org/toc/2150-7511ABSTRACT Small RNAs play a critical role in host-pathogen interaction. Indeed, small RNA-mediated silencing or RNA interference (RNAi) is one of the earliest forms of antiviral immunity. Although it represents the main defense system against viruses in many organisms, the antiviral role of RNAi has not been clearly proven in higher vertebrates. However, it is well established that their response to viral infection relies on the recognition of viral RNAs by host pattern recognition receptors (PRRs) to trigger activation of the interferon pathway. In the present work, we report the existence of a novel small noncoding RNA population produced in mammalian cells upon RNA virus infection. Using Sindbis virus (SINV) as a prototypic arbovirus model, we profiled the small RNA population of infected cells in both human and African green monkey cell lines. Here, we provide evidence for the presence of discrete small RNAs of viral origin that are not associated with the RNA-induced silencing complex (RISC), that are highly expressed and detected by Northern blot analysis, and that accumulate as 21- to 28-nucleotide (nt) species during infection. We report that the cellular antiviral endoribonuclease RNase L cleaves the viral genome, producing in turn the small RNAs. Surprisingly, we uncovered the presence of a modification on the 3′-end nucleotide of SINV-derived viral small RNAs (SvsRNAs) that might be at the origin of their stability. Altogether, our findings show that stable modified small viral RNAs could represent a novel way to modulate host-virus interaction upon SINV infection. IMPORTANCE In a continuous arms race, viruses have to deal with host antiviral responses in order to successfully establish an infection. In mammalian cells, the host defense mechanism relies on the recognition of viral RNAs, resulting in the activation of type I interferons (IFNs). In turn, the expression of many interferon-stimulated genes (ISGs) is induced to inhibit viral replication. Here we report that the cytoplasmic, interferon-induced, cellular endoribonuclease RNase L is involved in the accumulation of a novel small RNA population of viral origin. These small RNAs are produced upon SINV infection of mammalian cells and are stabilized by a 3′-end modification. Altogether, our findings indicate that in our system RNA silencing is not active against Sindbis virus (SINV) and might open the way to a better understanding of the antiviral response mediated by a novel class of small RNAs.Erika GirardiBéatrice Chane-Woon-MingMélanie MessmerPasi KaukinenSébastien PfefferAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 6 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Erika Girardi Béatrice Chane-Woon-Ming Mélanie Messmer Pasi Kaukinen Sébastien Pfeffer Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells
description	ABSTRACT Small RNAs play a critical role in host-pathogen interaction. Indeed, small RNA-mediated silencing or RNA interference (RNAi) is one of the earliest forms of antiviral immunity. Although it represents the main defense system against viruses in many organisms, the antiviral role of RNAi has not been clearly proven in higher vertebrates. However, it is well established that their response to viral infection relies on the recognition of viral RNAs by host pattern recognition receptors (PRRs) to trigger activation of the interferon pathway. In the present work, we report the existence of a novel small noncoding RNA population produced in mammalian cells upon RNA virus infection. Using Sindbis virus (SINV) as a prototypic arbovirus model, we profiled the small RNA population of infected cells in both human and African green monkey cell lines. Here, we provide evidence for the presence of discrete small RNAs of viral origin that are not associated with the RNA-induced silencing complex (RISC), that are highly expressed and detected by Northern blot analysis, and that accumulate as 21- to 28-nucleotide (nt) species during infection. We report that the cellular antiviral endoribonuclease RNase L cleaves the viral genome, producing in turn the small RNAs. Surprisingly, we uncovered the presence of a modification on the 3′-end nucleotide of SINV-derived viral small RNAs (SvsRNAs) that might be at the origin of their stability. Altogether, our findings show that stable modified small viral RNAs could represent a novel way to modulate host-virus interaction upon SINV infection. IMPORTANCE In a continuous arms race, viruses have to deal with host antiviral responses in order to successfully establish an infection. In mammalian cells, the host defense mechanism relies on the recognition of viral RNAs, resulting in the activation of type I interferons (IFNs). In turn, the expression of many interferon-stimulated genes (ISGs) is induced to inhibit viral replication. Here we report that the cytoplasmic, interferon-induced, cellular endoribonuclease RNase L is involved in the accumulation of a novel small RNA population of viral origin. These small RNAs are produced upon SINV infection of mammalian cells and are stabilized by a 3′-end modification. Altogether, our findings indicate that in our system RNA silencing is not active against Sindbis virus (SINV) and might open the way to a better understanding of the antiviral response mediated by a novel class of small RNAs.
format	article
author	Erika Girardi Béatrice Chane-Woon-Ming Mélanie Messmer Pasi Kaukinen Sébastien Pfeffer
author_facet	Erika Girardi Béatrice Chane-Woon-Ming Mélanie Messmer Pasi Kaukinen Sébastien Pfeffer
author_sort	Erika Girardi
title	Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells
title_short	Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells
title_full	Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells
title_fullStr	Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells
title_full_unstemmed	Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells
title_sort	identification of rnase l-dependent, 3′-end-modified, viral small rnas in sindbis virus-infected mammalian cells
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/e6b1ce8553864c5da1f666e2f8bf580b
work_keys_str_mv	AT erikagirardi identificationofrnaseldependent3endmodifiedviralsmallrnasinsindbisvirusinfectedmammaliancells AT beatricechanewoonming identificationofrnaseldependent3endmodifiedviralsmallrnasinsindbisvirusinfectedmammaliancells AT melaniemessmer identificationofrnaseldependent3endmodifiedviralsmallrnasinsindbisvirusinfectedmammaliancells AT pasikaukinen identificationofrnaseldependent3endmodifiedviralsmallrnasinsindbisvirusinfectedmammaliancells AT sebastienpfeffer identificationofrnaseldependent3endmodifiedviralsmallrnasinsindbisvirusinfectedmammaliancells
_version_	1718427617336492032

Identification of RNase L-Dependent, 3′-End-Modified, Viral Small RNAs in Sindbis Virus-Infected Mammalian Cells

Ejemplares similares