Publications

1.

Chaohui Lin, Edmund Osei Kuffour, Nina V Fuchs, Christoph G W Gertzen, Jesko Kaiser, Maximilian Hirschenberger, Xiao Tang, Haifeng C Xu, Oliver Michel, Ronny Tao, Alexandra Haase, Ulrich Martin, Thomas Kurz, Ingo Drexler, Boris Görg, Philipp A Lang, Tom Luedde, Konstantin M J Sparrer, Holger Gohlke, Renate König, Carsten Münk

Regulation of STING activity in DNA sensing by ISG15 modification Journal Article

In: Cell Rep, vol. 42, no. 11, pp. 113277, 2023, ISSN: 2211 – 1247.

Abstract | Links

2.

Moritz Schüssler, Kerstin Schott, Nina Verena Fuchs, Adrian Oo, Morssal Zahadi, Paula Rauch, Baek Kim, Renate König

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

2023.

Abstract | Links

@misc{pmid37662193,

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

author = {Moritz Schüssler and Kerstin Schott and Nina Verena Fuchs and Adrian Oo and Morssal Zahadi and Paula Rauch and Baek Kim and Renate König},

doi = {10.1101/2023.08.24.554731},

year  = {2023},

date = {2023-08-01},

journal = {bioRxiv},

abstract = {Sterile α motif (SAM) and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphate triphosphohydrolase (dNTPase) and a potent restriction factor for immunodeficiency virus 1 (HIV-1), active in myeloid and resting CD4 T cells. The anti-viral activity of SAMHD1 is regulated by dephosphorylation of the residue T592. However, the impact of T592 phosphorylation on dNTPase activity is still under debate. Whether additional cellular functions of SAMHD1 impact anti-viral restriction is not completely understood. We report BLaER1 cells as a novel human macrophage HIV-1 infection model combined with CRISPR/Cas9 knock-in (KI) introducing specific mutations into the  locus to study mutations in a physiological context. Transdifferentiated BLaER1 cells harbor active dephosphorylated SAMHD1 that blocks HIV-1 reporter virus infection. As expected, homozygous T592E mutation, but not T592A, relieved a block to HIV-1 reverse transcription. Co-delivery of VLP-Vpx to SAMHD1 T592E KI mutant cells did not further enhance HIV-1 infection indicating the absence of an additional SAMHD1-mediated antiviral activity independent of T592 de-phosphorylation. T592E KI cells retained dNTP levels similar to WT cells indicating uncoupling of anti-viral and dNTPase activity of SAMHD1. The integrity of the catalytic site in SAMHD1 was critical for anti-viral activity, yet poor correlation of HIV-1 restriction and global cellular dNTP levels was observed in cells harboring catalytic core mutations. Together, we emphasize the complexity of the relationship between HIV-1 restriction, SAMHD1 enzymatic function and T592 phospho-regulation and provide novel tools for investigation in an endogenous and physiological context.},

keywords = {},

pubstate = {published},

tppubtype = {misc}

}

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Sterile α motif (SAM) and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphate triphosphohydrolase (dNTPase) and a potent restriction factor for immunodeficiency virus 1 (HIV‑1), active in myeloid and resting CD4 T cells. The anti-viral activity of SAMHD1 is regulated by dephosphorylation of the residue T592. However, the impact of T592 phosphorylation on dNTPase activity is still under debate. Whether additional cellular functions of SAMHD1 impact anti-viral restriction is not completely understood. We report BLaER1 cells as a novel human macrophage HIV‑1 infection model combined with CRISPR/Cas9 knock-in (KI) introducing specific mutations into the locus to study mutations in a physiological context. Transdifferentiated BLaER1 cells harbor active dephosphorylated SAMHD1 that blocks HIV‑1 reporter virus infection. As expected, homozygous T592E mutation, but not T592A, relieved a block to HIV‑1 reverse transcription. Co-delivery of VLP-Vpx to SAMHD1 T592E KI mutant cells did not further enhance HIV‑1 infection indicating the absence of an additional SAMHD1-mediated antiviral activity independent of T592 de-phosphorylation. T592E KI cells retained dNTP levels similar to WT cells indicating uncoupling of anti-viral and dNTPase activity of SAMHD1. The integrity of the catalytic site in SAMHD1 was critical for anti-viral activity, yet poor correlation of HIV‑1 restriction and global cellular dNTP levels was observed in cells harboring catalytic core mutations. Together, we emphasize the complexity of the relationship between HIV‑1 restriction, SAMHD1 enzymatic function and T592 phospho-regulation and provide novel tools for investigation in an endogenous and physiological context.

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3.

Hussein Al-Shehabi, Norbert Bannert

PERV induces CXCL10 in human monocytes and monocyte-derived primary cells. Journal Article

In: online ahead of print, 2022, ISSN: 1423 – 0100.