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bioRxiv · 10.1101/2024.04.02.587611

Multilayered interaction between CRISPR-Cas subtype I-A and adjacently encoded Acrs of virus SIRV2

Bhoobalan-Chitty, Y.·Dwiputra, N.·Mayo-Munoz, D.·Baadsgaard, K.·Detlefsen, M. R. K. S.·Peng, X.
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Abstract

Among the >100 anti-CRISPRs (Acrs) identified to date, the vast majority inhibit CRISPR-Cas immunity on its own. Here we report a multilayered interaction between CRISPR-Cas subtype I-A immunity and two Acrs encoded adjacently in the genome of Saccharolobus virus SIRV2, gp47 (AcrIA3) and gp48 (previously known as AcrIIIB1, hence termed AcrIIIB1/AcrIA4). The host subtype I-A CRISPR-Cas interference module was shown previously to be up-regulated upon SIRV2 infection, through the release of transcriptional repressor Csa3b from the promoter. We demonstrate that AcrIIIB1/AcrIA4 on its own increases viral infectivity 4-5 orders of magnitude in the presence of the host subtype I-A CRISPR-Cas immunity. This Acr is able to completely inhibit the subtype I-A CRISPR-Cas immunity when the transcriptional activation of the latter is artificially removed, suggesting that Acrs might be one of the driving forces for the evolution of CRISPR-Cas up-regulation. Interestingly, AcrIA3 cooperates with AcrIIIB1/AcrIA4 by inhibiting transcriptional activation of the host subtype I-A CRISPR-Cas interference module through interaction with the promoter of the latter. Taken together, our data shed light on how virus-host arms race shaped the evolution of CRISPR-Cas and Acrs.

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Bhoobalan-Chitty, Y., Dwiputra, N., Mayo-Munoz, D., Baadsgaard, K., Detlefsen, M. R. K. S., Peng, X.. 2024-04-02. Multilayered interaction between CRISPR-Cas subtype I-A and adjacently encoded Acrs of virus SIRV2. https://doi.org/10.1101/2024.04.02.587611

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