@article{mbs:/content/journal/jgv/10.1099/jgv.0.001232, author = "Al-Shehabi, Hussein and Fiebig, Uwe and Kutzner, Juliane and Denner, Joachim and Schaller, Torsten and Bannert, Norbert and Hofmann, Henning", title = "Human SAMHD1 restricts the xenotransplantation relevant porcine endogenous retrovirus (PERV) in non-dividing cells", journal= "Journal of General Virology", year = "2019", volume = "100", number = "4", pages = "656-661", doi = "https://doi.org/10.1099/jgv.0.001232", url = "https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001232", publisher = "Microbiology Society", issn = "1465-2099", type = "Journal Article", keywords = "Xenotransplantation", keywords = "PERV", keywords = "SAMHD1", abstract = "The release of porcine endogenous retrovirus (PERV) particles from pig cells is a potential risk factor during xenotransplantation by way of productively infecting the human transplant recipient. Potential countermeasures against PERV replication are restriction factors that block retroviral replication. SAMHD1 is a triphosphohydrolase that depletes the cellular pool of dNTPs in non-cycling cells starving retroviral reverse transcription. We investigated the antiviral activity of human SAMHD1 against PERV and found that SAMHD1 potently restricts its reverse transcription in human monocytes, monocyte-derived dendritic cells (MDDC), or macrophages (MDM) and in monocytic THP-1 cells. Degradation of SAMHD1 by SIVmac Vpx or CRISPR/Cas9 knock-out of SAMHD1 allowed for PERV reverse transcription. Addition of deoxynucleosides alleviated the SAMHD1-mediated restriction suggesting that SAMHD1-mediated degradation of dNTPs restricts PERV replication in these human immune cells. In conclusion, our findings highlight SAMHD1 as a potential barrier to PERV transmission from pig transplants to human recipients during xenotransplantation.", }