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Gene editing of SAMHD1 in macrophage-like cells reveals complex relationships between SAMHD1 phospho-regulation, HIV-1 restriction and cellular dNTP levels.

Moritz SchüsslerKerstin SchottNina Verena FuchsAdrian OoMorssal ZahadiPaula RauchBaek KimRenate König
Published in: bioRxiv : the preprint server for biology (2023)
We introduce BLaER1 cells as an alternative myeloid cell model in combination with CRISPR/Cas9-mediated gene editing to study the influence of SAMHD1 T592 Mophosphorylation on anti-viral restriction and the control of cellular dNTP levels in an endogenous, physiological relevant context. Proper understanding of the mechanism of the anti-viral function of SAMHD1 will provide attractive strategies aiming at selectively manipulating SAMHD1 without affecting other cellular functions.Even more, our toolkit may inspire further genetic analysis and investigation of restriction factors inhibiting retroviruses, their cellular function and regulation, leading to a deeper understanding of intrinsic anti-viral immunity.
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