An Alternative STAT Signaling Pathway Acts in Viral Immunity in <italic toggle="yes">Caenorhabditis elegans</italic>

ABSTRACT Across metazoans, innate immunity is vital in defending organisms against viral infection. In mammals, antiviral innate immunity is orchestrated by interferon signaling, activating the STAT transcription factors downstream of the JAK kinases to induce expression of antiviral effector genes....

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Autores principales:	Mélanie Tanguy, Louise Véron, Przemyslaw Stempor, Julie Ahringer, Peter Sarkies, Eric A. Miska
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Caenorhabditis elegans Orsay virus RNA virus STAT signaling innate immunity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/72f7072ee65a4bd289ec7ce1cc88057a
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spelling	oai:doaj.org-article:72f7072ee65a4bd289ec7ce1cc88057a2021-11-15T15:51:51ZAn Alternative STAT Signaling Pathway Acts in Viral Immunity in <italic toggle="yes">Caenorhabditis elegans</italic>10.1128/mBio.00924-172150-7511https://doaj.org/article/72f7072ee65a4bd289ec7ce1cc88057a2017-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00924-17https://doaj.org/toc/2150-7511ABSTRACT Across metazoans, innate immunity is vital in defending organisms against viral infection. In mammals, antiviral innate immunity is orchestrated by interferon signaling, activating the STAT transcription factors downstream of the JAK kinases to induce expression of antiviral effector genes. In the nematode Caenorhabditis elegans, which lacks the interferon system, the major antiviral response so far described is RNA interference (RNAi), but whether additional gene expression responses are employed is not known. Here we show that, despite the absence of both interferon and JAK, the C. elegans STAT homolog STA-1 orchestrates antiviral immunity. Intriguingly, mutants lacking STA-1 are less permissive to antiviral infection. Using gene expression analysis and chromatin immunoprecipitation, we show that, in contrast to the mammalian pathway, STA-1 acts mostly as a transcriptional repressor. Thus, STA-1 might act to suppress a constitutive antiviral response in the absence of infection. Additionally, using a reverse genetic screen, we identify the kinase SID-3 as a new component of the response to infection, which, along with STA-1, participates in the transcriptional regulatory network of the immune response. Our work uncovers novel physiological roles for two factors in viral infection: a SID protein acting independently of RNAi and a STAT protein acting in C. elegans antiviral immunity. Together, these results illustrate the complex evolutionary trajectory displayed by innate immune signaling pathways across metazoan organisms. IMPORTANCE Since innate immunity was discovered, a diversity of pathways has arisen as powerful first-line defense mechanisms to fight viral infection. RNA interference, reported mostly in invertebrates and plants, as well as the mammalian interferon response and JAK/STAT pathway are key in RNA virus innate immunity. We studied infection by the Orsay virus in Caenorhabditis elegans, where RNAi is known to be a potent antiviral defense. We show that, in addition to its RNAi pathway, C. elegans utilizes an alternative STAT pathway to control the levels of viral infection. We identify the transcription factor STA-1 and the kinase SID-3 as two components of this response. Our study defines C. elegans as a new example of the diversity of antiviral strategies.Mélanie TanguyLouise VéronPrzemyslaw StemporJulie AhringerPeter SarkiesEric A. MiskaAmerican Society for MicrobiologyarticleCaenorhabditis elegansOrsay virusRNA virusSTAT signalinginnate immunityMicrobiologyQR1-502ENmBio, Vol 8, Iss 5 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Caenorhabditis elegans Orsay virus RNA virus STAT signaling innate immunity Microbiology QR1-502
spellingShingle	Caenorhabditis elegans Orsay virus RNA virus STAT signaling innate immunity Microbiology QR1-502 Mélanie Tanguy Louise Véron Przemyslaw Stempor Julie Ahringer Peter Sarkies Eric A. Miska An Alternative STAT Signaling Pathway Acts in Viral Immunity in <italic toggle="yes">Caenorhabditis elegans</italic>
description	ABSTRACT Across metazoans, innate immunity is vital in defending organisms against viral infection. In mammals, antiviral innate immunity is orchestrated by interferon signaling, activating the STAT transcription factors downstream of the JAK kinases to induce expression of antiviral effector genes. In the nematode Caenorhabditis elegans, which lacks the interferon system, the major antiviral response so far described is RNA interference (RNAi), but whether additional gene expression responses are employed is not known. Here we show that, despite the absence of both interferon and JAK, the C. elegans STAT homolog STA-1 orchestrates antiviral immunity. Intriguingly, mutants lacking STA-1 are less permissive to antiviral infection. Using gene expression analysis and chromatin immunoprecipitation, we show that, in contrast to the mammalian pathway, STA-1 acts mostly as a transcriptional repressor. Thus, STA-1 might act to suppress a constitutive antiviral response in the absence of infection. Additionally, using a reverse genetic screen, we identify the kinase SID-3 as a new component of the response to infection, which, along with STA-1, participates in the transcriptional regulatory network of the immune response. Our work uncovers novel physiological roles for two factors in viral infection: a SID protein acting independently of RNAi and a STAT protein acting in C. elegans antiviral immunity. Together, these results illustrate the complex evolutionary trajectory displayed by innate immune signaling pathways across metazoan organisms. IMPORTANCE Since innate immunity was discovered, a diversity of pathways has arisen as powerful first-line defense mechanisms to fight viral infection. RNA interference, reported mostly in invertebrates and plants, as well as the mammalian interferon response and JAK/STAT pathway are key in RNA virus innate immunity. We studied infection by the Orsay virus in Caenorhabditis elegans, where RNAi is known to be a potent antiviral defense. We show that, in addition to its RNAi pathway, C. elegans utilizes an alternative STAT pathway to control the levels of viral infection. We identify the transcription factor STA-1 and the kinase SID-3 as two components of this response. Our study defines C. elegans as a new example of the diversity of antiviral strategies.
format	article
author	Mélanie Tanguy Louise Véron Przemyslaw Stempor Julie Ahringer Peter Sarkies Eric A. Miska
author_facet	Mélanie Tanguy Louise Véron Przemyslaw Stempor Julie Ahringer Peter Sarkies Eric A. Miska
author_sort	Mélanie Tanguy
title	An Alternative STAT Signaling Pathway Acts in Viral Immunity in <italic toggle="yes">Caenorhabditis elegans</italic>
title_short	An Alternative STAT Signaling Pathway Acts in Viral Immunity in <italic toggle="yes">Caenorhabditis elegans</italic>
title_full	An Alternative STAT Signaling Pathway Acts in Viral Immunity in <italic toggle="yes">Caenorhabditis elegans</italic>
title_fullStr	An Alternative STAT Signaling Pathway Acts in Viral Immunity in <italic toggle="yes">Caenorhabditis elegans</italic>
title_full_unstemmed	An Alternative STAT Signaling Pathway Acts in Viral Immunity in <italic toggle="yes">Caenorhabditis elegans</italic>
title_sort	alternative stat signaling pathway acts in viral immunity in <italic toggle="yes">caenorhabditis elegans</italic>
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/72f7072ee65a4bd289ec7ce1cc88057a
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An Alternative STAT Signaling Pathway Acts in Viral Immunity in <italic toggle="yes">Caenorhabditis elegans</italic>

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