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Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice

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Abstract

Animal donors such as pigs could provide an alternative source of organs for transplantation. However, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection1,2. All pigs contain several copies of porcine endogenous retroviruses (PERV)3,4, and at least three variants of PERV can infect human cell lines in vitro in co-culture, infectivity and pseudotyping experiments3,5,6,7. Thus, if xenotransplantation of pig tissues results in PERV viral replication, there is a risk of spreading and adaptation of this retrovirus to the human host. C-type retroviruses related to PERV are associated with malignancies of haematopoietic lineage cells in their natural hosts8. Here we show that pig pancreatic islets produce PERV and can infect human cells in culture. After transplantation into NOD/SCID (non-obese diabetic, severe combined immunodeficiency) mice, we detect ongoing viral expression and several tissue compartments become infected. This is the first evidence that PERV is transcriptionally active and infectious cross-species in vivo after transplantation of pig tissues. These results show that a concern for PERV infection risk associated with pig islet xenotransplantation in immunosuppressed human patients may be justified.

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Figure 1: Pig islets release infectious PERV virions and productively infect human U293 cells.
Figure 2: PERV expression in pig islets after transplantation.

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Acknowledgements

We thank J. Elder, A. Pelletier, J. Coffin, J. Stoye and G. Langford for helpful discussions, and D. Stablein for expert statistical advice. We thank I. Mychkovsky and T. Gladden for assistance in mRNA/DNA purification, T. Gilmore, J. Ansite and D. Scharpe for assistance in purification of pig islets, and L. Crisa, P. Hildbrand and O. Schussler for help with mouse surgery. We thank R. Ingram and M. Pierschbacher for the RGD collagen templates for transplantation. D.R.S, B.C.G., F.S.F., B.E.T. and this work are supported by an NIH/NIAID grant. L.J.W.L. is supported by a Juvenile Diabetes Foundation International (JDFI) fellowship.

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Authors and Affiliations

  1. The Scripps Research Institute Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, 92037, California, USA

    Luc J.W. van der Laan, Bradley C. Griffeth, Francine S. Frasier, Bruce E. Torbett & Daniel R. Salomon

  2. Genetic Therapy Inc., A Novartis Company , 9 West Watkins Mill Road, Gaithersburg, 20878, Maryland, USA

    Christopher Lockey, Zhifeng Long & Edward Otto

  3. Food and Drug Administration, Centre for Biologics Evaluation and Research, 8800 Rockville Pike, Bethesda, 20892, Maryland, USA

    Carolyn A. Wilson

  4. Department of Veterinary Pathology, University of Glasgow, Bearsden Road, Glasgow , G61 1QH, Scotland

    David E. Onions

  5. Q-One Biotech Ltd , Todd Campus, Glasgow, G20 OXA, UK

    David E. Onions

  6. Department of Surgery, University of Minnesota, 420 Delaware Street S.E., Minneapolis , 55455, Minnesota, USA

    Bernhard J. Hering

Authors
  1. Luc J.W. van der Laan
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  2. Christopher Lockey
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  3. Bradley C. Griffeth
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  4. Francine S. Frasier
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  5. Carolyn A. Wilson
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  6. David E. Onions
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  7. Bernhard J. Hering
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  8. Zhifeng Long
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  9. Edward Otto
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  10. Bruce E. Torbett
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  11. Daniel R. Salomon
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Correspondence to Daniel R. Salomon.

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van der Laan, L., Lockey, C., Griffeth, B. et al. Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice. Nature 407, 90–94 (2000). https://doi.org/10.1038/35024089

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  • DOI: https://doi.org/10.1038/35024089

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