Human SAMHD1 restricts the xenotransplantation relevant porcine endogenous retrovirus (PERV) in non-dividing cells
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 replica...
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| Main Authors: | , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 February 2019
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| In: |
Journal of general virology
Year: 2019, Volume: 100, Issue: 4, Pages: 656-661 |
| ISSN: | 1465-2099 |
| DOI: | 10.1099/jgv.0.001232 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1099/jgv.0.001232 Verlag: https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.001232 
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| Author Notes: | Hussein Al-Shehabi, Uwe Fiebig, Juliane Kutzner, Joachim Denner, Torsten Schaller, Norbert Bannert, Henning Hofmann |
| Summary: | 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., |
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| Item Description: | Gesehen am 29.01.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1465-2099 |
| DOI: | 10.1099/jgv.0.001232 |