The antiviral state has shaped the CpG composition of the vertebrate interferome to avoid self-targeting.

Antiviral defenses can sense viral RNAs and mediate their destruction. This presents a challenge for host cells since they must destroy viral RNAs while sparing the host mRNAs that encode antiviral effectors. Here, we show that highly upregulated interferon-stimulated genes (ISGs), which encode anti...

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Autores principales:	Andrew E Shaw, Suzannah J Rihn, Nardus Mollentze, Arthur Wickenhagen, Douglas G Stewart, Richard J Orton, Srikeerthana Kuchi, Siddharth Bakshi, Mila Rodriguez Collados, Matthew L Turnbull, Joseph Busby, Quan Gu, Katherine Smollett, Connor G G Bamford, Elena Sugrue, Paul C D Johnson, Ana Filipe Da Silva, Alfredo Castello, Daniel G Streicker, David L Robertson, Massimo Palmarini, Sam J Wilson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/93c6a324bb0649b4bf2748908f349e90
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spelling	oai:doaj.org-article:93c6a324bb0649b4bf2748908f349e902021-12-02T19:54:37ZThe antiviral state has shaped the CpG composition of the vertebrate interferome to avoid self-targeting.1544-91731545-788510.1371/journal.pbio.3001352https://doaj.org/article/93c6a324bb0649b4bf2748908f349e902021-09-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001352https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Antiviral defenses can sense viral RNAs and mediate their destruction. This presents a challenge for host cells since they must destroy viral RNAs while sparing the host mRNAs that encode antiviral effectors. Here, we show that highly upregulated interferon-stimulated genes (ISGs), which encode antiviral proteins, have distinctive nucleotide compositions. We propose that self-targeting by antiviral effectors has selected for ISG transcripts that occupy a less self-targeted sequence space. Following interferon (IFN) stimulation, the CpG-targeting antiviral effector zinc-finger antiviral protein (ZAP) reduces the mRNA abundance of multiple host transcripts, providing a mechanistic explanation for the repression of many (but not all) interferon-repressed genes (IRGs). Notably, IRGs tend to be relatively CpG rich. In contrast, highly upregulated ISGs tend to be strongly CpG suppressed. Thus, ZAP is an example of an effector that has not only selected compositional biases in viral genomes but also appears to have notably shaped the composition of host transcripts in the vertebrate interferome.Andrew E ShawSuzannah J RihnNardus MollentzeArthur WickenhagenDouglas G StewartRichard J OrtonSrikeerthana KuchiSiddharth BakshiMila Rodriguez ColladosMatthew L TurnbullJoseph BusbyQuan GuKatherine SmollettConnor G G BamfordElena SugruePaul C D JohnsonAna Filipe Da SilvaAlfredo CastelloDaniel G StreickerDavid L RobertsonMassimo PalmariniSam J WilsonPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 9, p e3001352 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Andrew E Shaw Suzannah J Rihn Nardus Mollentze Arthur Wickenhagen Douglas G Stewart Richard J Orton Srikeerthana Kuchi Siddharth Bakshi Mila Rodriguez Collados Matthew L Turnbull Joseph Busby Quan Gu Katherine Smollett Connor G G Bamford Elena Sugrue Paul C D Johnson Ana Filipe Da Silva Alfredo Castello Daniel G Streicker David L Robertson Massimo Palmarini Sam J Wilson The antiviral state has shaped the CpG composition of the vertebrate interferome to avoid self-targeting.
description	Antiviral defenses can sense viral RNAs and mediate their destruction. This presents a challenge for host cells since they must destroy viral RNAs while sparing the host mRNAs that encode antiviral effectors. Here, we show that highly upregulated interferon-stimulated genes (ISGs), which encode antiviral proteins, have distinctive nucleotide compositions. We propose that self-targeting by antiviral effectors has selected for ISG transcripts that occupy a less self-targeted sequence space. Following interferon (IFN) stimulation, the CpG-targeting antiviral effector zinc-finger antiviral protein (ZAP) reduces the mRNA abundance of multiple host transcripts, providing a mechanistic explanation for the repression of many (but not all) interferon-repressed genes (IRGs). Notably, IRGs tend to be relatively CpG rich. In contrast, highly upregulated ISGs tend to be strongly CpG suppressed. Thus, ZAP is an example of an effector that has not only selected compositional biases in viral genomes but also appears to have notably shaped the composition of host transcripts in the vertebrate interferome.
format	article
author	Andrew E Shaw Suzannah J Rihn Nardus Mollentze Arthur Wickenhagen Douglas G Stewart Richard J Orton Srikeerthana Kuchi Siddharth Bakshi Mila Rodriguez Collados Matthew L Turnbull Joseph Busby Quan Gu Katherine Smollett Connor G G Bamford Elena Sugrue Paul C D Johnson Ana Filipe Da Silva Alfredo Castello Daniel G Streicker David L Robertson Massimo Palmarini Sam J Wilson
author_facet	Andrew E Shaw Suzannah J Rihn Nardus Mollentze Arthur Wickenhagen Douglas G Stewart Richard J Orton Srikeerthana Kuchi Siddharth Bakshi Mila Rodriguez Collados Matthew L Turnbull Joseph Busby Quan Gu Katherine Smollett Connor G G Bamford Elena Sugrue Paul C D Johnson Ana Filipe Da Silva Alfredo Castello Daniel G Streicker David L Robertson Massimo Palmarini Sam J Wilson
author_sort	Andrew E Shaw
title	The antiviral state has shaped the CpG composition of the vertebrate interferome to avoid self-targeting.
title_short	The antiviral state has shaped the CpG composition of the vertebrate interferome to avoid self-targeting.
title_full	The antiviral state has shaped the CpG composition of the vertebrate interferome to avoid self-targeting.
title_fullStr	The antiviral state has shaped the CpG composition of the vertebrate interferome to avoid self-targeting.
title_full_unstemmed	The antiviral state has shaped the CpG composition of the vertebrate interferome to avoid self-targeting.
title_sort	antiviral state has shaped the cpg composition of the vertebrate interferome to avoid self-targeting.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/93c6a324bb0649b4bf2748908f349e90
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The antiviral state has shaped the CpG composition of the vertebrate interferome to avoid self-targeting.

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