1Department of HIV and other Retroviruses, Robert Koch Institute, Berlin, Germany.
2Department of Infectious Diseases, Virology, University Hospital Heidelberg, Heidelberg, Germany.
J Gen Virol. 2019 Apr;100(4):656-661. doi: 10.1099/jgv.0.001232. Epub 2019 Feb 15.
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.
猪内源性逆转录病毒 (PERV) 颗粒从猪细胞中释放出来是异种移植过程中的一个潜在风险因素，可能通过感染人类移植受者而产生感染。针对 PERV 复制的潜在对策是限制因子，可阻断逆转录病毒的复制。SAMHD1 是一种三磷酸水解酶，可耗尽非循环细胞中细胞内 dNTP 池，从而阻止逆转录病毒逆转录。我们研究了人 SAMHD1 对 PERV 的抗病毒活性，发现 SAMHD1 可有效抑制人单核细胞、单核细胞衍生的树突状细胞 (MDDC) 或巨噬细胞 (MDM) 以及单核细胞 THP-1 细胞中的 PERV 逆转录。SIVmac Vpx 降解 SAMHD1 或 CRISPR/Cas9 敲除 SAMHD1 允许 PERV 逆转录。添加脱氧核苷可缓解 SAMHD1 介导的限制，表明 SAMHD1 介导的 dNTP 降解可限制这些人免疫细胞中的 PERV 复制。总之，我们的发现强调了 SAMHD1 作为异种移植过程中从猪移植物向人类受者传播 PERV 的潜在障碍。
