Conservation of antiviral systems across domains of life reveals novel immune mechanisms in humans

Cury, Jean; Mordret, Ernest; Hernandez-Trejo, Veronica; Tesson, Florian; Ofir, Gal; Poirier, Enzo Z.; Bernheim, Aude

doi:10.1101/2022.12.12.520048

Cited by 15 publications

(16 citation statements)

References 48 publications

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“…However, the recent expansion of the known repertoire of anti-phage systems now provides the opportunity to apply the reverse reasoning, i.e. to translate our knowledge of prokaryotic immunity into the eukaryotic world 8,14,15,37 .…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, multiple eukaryotic innate immunity pathways have been shown to have a deep evolutionary origin in prokaryotes 1,14 . Many of the discoveries showing that bacterial defense systems function similarly to their eukaryotic counterparts were enabled by translating prior knowledge of eukaryotic immunity into the prokaryotic world.…”

Section: Discussionmentioning

confidence: 99%

“…e . to translate our knowledge of prokaryotic immunity into the eukaryotic world 8,14,15,37 . Our discovery of a new immune effector domain that is conserved across the tree of life presents an opportunity to unravel previously unknown functions within the innate immune system of eukaryotes based on bacterial defense against phages.…”

Section: Discussionmentioning

confidence: 99%

“…It was recently shown that multiple components of the cell-autonomous innate immune system of animals are also conserved in bacteria, where they function to protect against phage infection 1 . Such conserved immune components include the cGAS-STING pathway [2][3][4] , NOD-like receptors (NLRs) 5,6 , gasderminmediated pyroptosis 7 , Toll/interleukin-1 receptor (TIR) domain signaling 8,9 , the RNAi pathway 10,11 , SAMHD1 12 , viperins 13 , and others 14 . Based on these discoveries, it was shown that studying the immune system of bacteria can generate functional knowledge on previously unknown eukaryotic immune mechanisms 8,14,15 .…”

Section: Introductionmentioning

confidence: 99%

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A conserved family of immune effectors cleaves cellular ATP upon viral infection

Rousset

Yirmiya

Nesher

et al. 2023

Preprint

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During viral infection, cells can deploy immune strategies that deprive viruses of molecules essential for their replication. In this study, we report a family of immune effectors in bacteria which, in response to phage infection, degrade cellular ATP and dATP by cleaving the N-glycosidic bond between the adenine and sugar moieties. These ATP nucleosidase effectors are widely distributed within multiple bacterial defense systems including CBASS, prokaryotic argonautes and NLR-like proteins, and we show that degradation of (d)ATP during infection halts phage propagation and aborts infection. By analyzing homologs of the immune ATP nucleosidase domain, we discover and characterize Detocs, a new family of bacterial defense systems with a two-component phosphotransfer signaling architecture. The immune ATP nucleosidase domain is also encoded within a diverse set of eukaryotic proteins that have immune-like architectures, and we show biochemically that these eukaryotic homologs preserve the ATP nucleosidase activity. Our findings suggest that ATP and dATP degradation is a cell-autonomous innate immune strategy conserved across the tree of life.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A conserved family of immune effectors cleaves cellular ATP upon viral infection

Rousset

Yirmiya

Nesher

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Another DS of interest is Mokosh, which degrades foreign viral transcripts to protect cells from infections 8 . Mokosh system proteins (MkoA and MkoB) have domain homology to the anti-transposon piRNA (PIWI-interacting RNA) pathway in eukaryotes 5 . Our phylogenetic analysis of MkoA suggests a bacterial origin of this protein.…”

Section: Figurementioning

confidence: 99%

Asgard archaea defense systems and their roles in the origin of immunity in eukaryotes

Leao,

Little,

Appler

et al. 2023

Preprint

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Immune systems are integral to survival against viral infection. Recently, dozens of new anti-viral systems have been characterized in bacteria1. Some of these systems are present in eukaryotes and appear to have originated in prokaryotes. However, little is known about these defense mechanisms in archaea. Here, we identified 2,610 complete defense systems in archaea related to eukaryotes, the Asgardarchaeota2. These comprise 89 unique systems, including argonaute, NLR, mokosh, viperin, lassamu, and CBASS. Asgard viperin (asVip) and argonaute (asAgo) proteins are present at high frequencies compared to bacteria and have structural homology to eukaryotes. Phylogenetic analyses revealed asVips are ancestral eukaryotic proteins. Heterologous expression of asVips in bacteria, including the lineage closest to eukaryotes, Hodarchaeales, showed robust anti-phage activity. Eukaryotic-and bacterial-argonaute proteins appear to have originated in the Asgardarchaeota, and have ancient structural characteristics. AsAgos appear to have argonaute-PIWI domains which are key components of the RNA interference (RNAi) in eukaryotes. Characterization of hundreds of new defense systems in the Asgardarchaeota revealed these archaea played important roles in the innovation of viral protection in eukaryotes. Given their relationship to eukaryotes, these defense systems may have applications in biomedicine and biotechnology.

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Asgard archaea defense systems and their roles in the origin of eukaryotic immunity

Leão,

Little,

Appler

et al. 2024

Nat Commun

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Dozens of new antiviral systems have been recently characterized in bacteria. Some of these systems are present in eukaryotes and appear to have originated in prokaryotes, but little is known about these defense mechanisms in archaea. Here, we explore the diversity and distribution of defense systems in archaea and identify 2610 complete systems in Asgardarchaeota, a group of archaea related to eukaryotes. The Asgard defense systems comprise 89 unique systems, including argonaute, NLR, Mokosh, viperin, Lassamu, and CBASS. Asgard viperin and argonaute proteins have structural homology to eukaryotic proteins, and phylogenetic analyses suggest that eukaryotic viperin proteins were derived from Asgard viperins. We show that Asgard viperins display anti-phage activity when heterologously expressed in bacteria. Eukaryotic and bacterial argonaute proteins appear to have originated in Asgardarchaeota, and Asgard argonaute proteins have argonaute-PIWI domains, key components of eukaryotic RNA interference systems. Our results support that Asgardarchaeota played important roles in the origin of antiviral defense systems in eukaryotes.

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Conservation of antiviral systems across domains of life reveals novel immune mechanisms in humans

Cited by 15 publications

References 48 publications

A conserved family of immune effectors cleaves cellular ATP upon viral infection

A conserved family of immune effectors cleaves cellular ATP upon viral infection

Asgard archaea defense systems and their roles in the origin of immunity in eukaryotes

Asgard archaea defense systems and their roles in the origin of eukaryotic immunity

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