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Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice

Nature volume 407, pages 9094 (07 September 2000) | Download Citation

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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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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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Affiliations

  1. *The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, California 92037, 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, Maryland 20878, USA

    • Christopher Lockey
    • , Zhifeng Long
    •  & Edward Otto
  3. ‡Food and Drug Administration, Centre for Biologics Evaluation and Research, 8800 Rockville Pike, Bethesda, Maryland 20892, USA

    • Carolyn A. Wilson
  4. §University of Glasgow, Department of Veterinary Pathology, Bearsden Road, Glasgow G61 1QH, Scotland & Q-One Biotech Ltd , Todd Campus, Glasgow G20 OXA, UK

    • David E. Onions
  5. University of Minnesota, Department of Surgery, 420 Delaware Street S.E., Minneapolis , Minnesota 55455, USA

    • Bernhard J. Hering

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Correspondence to Daniel R. Salomon.

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https://doi.org/10.1038/35024089

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