A cross-institutional Journal Club Initiative
A conserved family of immune effectors cleaves cellular ATP upon viral infection
Rousset, F et al. (BioRxiv) DOI: 10.1101/2023.01.24.525353
ATP nucleosidase immune effectors
Detocs bacterial defense systems
The authors report the discovery of a new family of immune effectors in bacteria, which, in response to phage infection, degrade cellular ATP and dATP. During infection, this degradation of (d)ATP limits phage replication and aborts infection, by cleaving the N-glycosidic bond between the adenine and sugar moieties. By analyzing homologs of the immune ATP nucleosidase domain, the authors characterize a two-component system named Detocs, a new family of bacterial defense systems. Detocs first domain senses an environmental signal, triggering phosphate transfer to a second Purine Nucleoside Phosphorylase (PNP) domain that degrades (d)ATP. It leads to a slowdown of viral transcription and replication and a perturbation of lysis timing. The immune ATP nucleosidase domain of Detocs is also encoded within a diverse set of eukaryotic proteins that have immune-like structures. The authors showed that these eukaryotic homologs preserve the ATP nucleosidase activity. It suggest that (d)ATP degradation is a cell-autonomous innate immune strategy conserved across many species.
● Further studies will be necessary to investigate the immune functions of Cap17-like ATP nucleosidases in eukaryotes. It may be interesting to demonstrate that the PNP domain has a direct antiviral effect in these immune proteins, and to identify their targets.
● I may be also interesting to investigate the mechanisms explaining that no activity was detected on other adenine-containing nucleotides or nucleosides.
Translating prior knowledge of eukaryotic immunity into prokaryotic systems allowed showing that many bacterial defense systems function similarly to their eukaryotic counterparts. Now, the recent characterization of many anti-phage systems provides the opportunity to apply the reverse reasoning, to identify if new prokaryotic immune systems are present in eukaryotes. This discovery of the new immune effector domain of Detocs, conserved across many species, is an opportunity to unravel previously unknown immune functions of eukaryotes based on anti-viral bacterial defense.
Reviewed by Guillaume Mestrallet as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai and the Kennedy Institute of Rheumatology, University of Oxford.