%0 Journal Article %A Al-Shehabi, Hussein %A Fiebig, Uwe %A Kutzner, Juliane %A Denner, Joachim %A Schaller, Torsten %A Bannert, Norbert %A Hofmann, Henning %T Human SAMHD1 restricts the xenotransplantation relevant porcine endogenous retrovirus (PERV) in non-dividing cells %D 2019 %J Journal of General Virology, %V 100 %N 4 %P 656-661 %@ 1465-2099 %R https://doi.org/10.1099/jgv.0.001232 %K Xenotransplantation %K PERV %K SAMHD1 %I Microbiology Society, %X 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. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001232