Biology subjects

Vassover, D.

Publications and source records attributed to Vassover, D..

2 recordsLinked to original sources

bioRxiv2025

A TIR-SAVED effector mediates antiviral immunity via a conserved host signal

Cyclic oligonucleotide-based anti-phage signalling systems (CBASS) are widespread prokaryotic antiviral defense mechanisms that function through coordinated cyclase-effector interactions. Upon sensing viral infection, the cyclase produces a signal molecule that activates effector function and causes cell dormancy or death. However, the evolutionary origins and functional independence of CBASS components remain unclear. Type II CBASS systems commonly employ TIR-SAVED domain effector proteins that deplete cellular NAD+ during viral infection. Here, we demonstrate that a TIR-SAVED effector protein can operate as a standalone antiviral defense, causing significant growth inhibition and approximately 50% viral clearance during infection in the complete absence of its cognate cyclase. Remarkably, we show that the TIR-SAVED effector can sense cyclic di-AMP, a conserved second messenger produced by the host diadenylate cyclase DacZ, when the canonical CBASS signal is absent. This antiviral activity was associated with depletion of cellular NAD+ and required intact conserved functional residues within both the TIR and SAVED domains. These findings reveal a novel mechanism of antiviral signalling that expands the functional repertoire of CBASS. They also provide insights into the modular evolution of complex prokaryotic immune systems, suggesting that what are now CBASS effectors might have evolved as independent defense components before being integrated into multi-protein systems.

microbiology↗

bioRxiv2024

An archaeal CBASS system eliminates viruses without killing the host cells

Many cyclic-oligonucleotide-based anti-phage signalling systems (CBASS) defend against viral infections by depleting cellular NAD+ levels, eventually leading to dormancy or death. This abortive infection strategy is beneficial in stopping fast lytic infections, as cells die before spreading the virus to neighbouring cells. However, in chronic viral infections, which often occur in archaea, abortive infection could be detrimental, as the cost of immunity may outweigh that of infection. Here we study an archaeal CBASS system (H-CBASS2) that was expressed in the model species Haloferax volcanii DS2 and Haloferax gibbonsii LR2-5. We show that the system provides protection to H. gibbonsii against a lytic tailed haloarchaeal virus HFTV1 by depleting NAD+, similar to what has been observed for lytic phages in bacteria. H-CBASS2 is also triggered, though with much slower activity, during infection with the chronic, non-lytic virus HFPV-1, and promotes virus clearance after several passages without killing host cells. Moreover, cells that clear the HFPV-1 infection become substantially more resistant to subsequent infections, due to mutations in envelope-associated proteins. Cell death by NAD+ depletion only occurs after a very long infection with HFPV-1 on solid medium. These findings suggest that the magnitude of H-CBASS2 response is somehow tuned to the infection type can benefit the host during non-lytic infections, potentially explaining why such systems are relatively common in archaea.

microbiology↗