Letters to Nature
Nature 407, 90-94 (7 September 2000) | doi:10.1038/35024089; Received 5 April 2000; Accepted 22 June 2000
Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice
Luc J.W. van der Laan1, Christopher Lockey2, Bradley C. Griffeth1, Francine S. Frasier1, Carolyn A. Wilson3, David E. Onions4, Bernhard J. Hering5, Zhifeng Long2, Edward Otto2, Bruce E. Torbett1 & Daniel R. Salomon1
- The Scripps Research Institute, Department of Molecular and Experimental Medicine, 10550 North Torrey Pines Road, La Jolla, California 92037, USA
- Genetic Therapy Inc., A Novartis Company , 9 West Watkins Mill Road, Gaithersburg, Maryland 20878, USA
- Food and Drug Administration, Centre for Biologics Evaluation and Research, 8800 Rockville Pike, Bethesda, Maryland 20892, USA
- University of Glasgow, Department of Veterinary Pathology, Bearsden Road, Glasgow G61 1QH, Scotland & Q-One Biotech Ltd , Todd Campus, Glasgow G20 OXA, UK
- University of Minnesota, Department of Surgery, 420 Delaware Street S.E., Minneapolis , Minnesota 55455, USA
Correspondence to: Daniel R. Salomon1 Correspondence and requests for materials should be addressed to: D.R.S. (email: Email: dsalomon@scripps.edu).
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.
