%0 Journal Article %1 nchioua2020finger %A Nchioua, Rayhane %A Kmiec, Dorota %A Mueller, Janis %A Conzelmann, Carina %A Gross, Ruediger %A Swanson, Chad M %A Neil, Stuart %A Stenger, Steffen %A Sauter, Daniel %A Muench, Jan %A Sparrer, Konstantin MJ %A Kirchhoff, Frank %D 2020 %I Cold Spring Harbor Laboratory %J bioRxiv %K antiviral covid-19 zinc %R 10.1101/2020.06.04.134379 %T The Zinc Finger Antiviral Protein restricts SARS-CoV-2 %U https://www.biorxiv.org/content/early/2020/06/04/2020.06.04.134379 %X Recent evidence shows that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly sensitive to interferons (IFNs). However, the underlying antiviral effectors remain to be defined. Here, we show that Zinc finger antiviral protein (ZAP) that specifically targets CpG dinucleotides in viral RNA sequences restricts SARS-CoV-2. We demonstrate that ZAP and its cofactors KHNYN and TRIM25 are expressed in human lung cells. Type I, II and III IFNs all strongly inhibited SARS-CoV-2 and further induced ZAP expression. Strikingly, SARS-CoV-2 and its closest relatives from bats show the strongest CpG suppression among all known human and bat coronaviruses, respectively. Nevertheless, knock-down of ZAP significantly increased SARS-CoV-2 production in lung cells, particularly upon treatment with IFN-alpha or IFN-gamma. Thus, our results identify ZAP as an effector of the IFN response against SARS-CoV-2, although this pandemic pathogen may be preadapted to the low CpG environment in humans.Competing Interest StatementThe authors have declared no competing interest.

@article{nchioua2020finger, abstract = {Recent evidence shows that the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is highly sensitive to interferons (IFNs). However, the underlying antiviral effectors remain to be defined. Here, we show that Zinc finger antiviral protein (ZAP) that specifically targets CpG dinucleotides in viral RNA sequences restricts SARS-CoV-2. We demonstrate that ZAP and its cofactors KHNYN and TRIM25 are expressed in human lung cells. Type I, II and III IFNs all strongly inhibited SARS-CoV-2 and further induced ZAP expression. Strikingly, SARS-CoV-2 and its closest relatives from bats show the strongest CpG suppression among all known human and bat coronaviruses, respectively. Nevertheless, knock-down of ZAP significantly increased SARS-CoV-2 production in lung cells, particularly upon treatment with IFN-alpha or IFN-gamma. Thus, our results identify ZAP as an effector of the IFN response against SARS-CoV-2, although this pandemic pathogen may be preadapted to the low CpG environment in humans.Competing Interest StatementThe authors have declared no competing interest.}, added-at = {2020-06-06T07:40:43.000+0200}, author = {Nchioua, Rayhane and Kmiec, Dorota and Mueller, Janis and Conzelmann, Carina and Gross, Ruediger and Swanson, Chad M and Neil, Stuart and Stenger, Steffen and Sauter, Daniel and Muench, Jan and Sparrer, Konstantin MJ and Kirchhoff, Frank}, biburl = {https://www.bibsonomy.org/bibtex/273125e48ef20451925fd308767373889/fordham1}, description = {The Zinc Finger Antiviral Protein restricts SARS-CoV-2 | bioRxiv}, doi = {10.1101/2020.06.04.134379}, elocation-id = {2020.06.04.134379}, eprint = {https://www.biorxiv.org/content/early/2020/06/04/2020.06.04.134379.full.pdf}, interhash = {8cc4e0a00511741883820723c9f87649}, intrahash = {73125e48ef20451925fd308767373889}, journal = {bioRxiv}, keywords = {antiviral covid-19 zinc}, publisher = {Cold Spring Harbor Laboratory}, timestamp = {2020-06-06T07:40:43.000+0200}, title = {The Zinc Finger Antiviral Protein restricts SARS-CoV-2}, url = {https://www.biorxiv.org/content/early/2020/06/04/2020.06.04.134379}, year = 2020 }