Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice

Luc J.W. van der Laan, Christopher Lockey, Bradley C. Griffeth, Francine S. Frasier, Carolyn A. Wilson, David E. Onions, Bernhard J. Hering, Zhifeng Long, Edward Otto, Bruce E. Torbett and Daniel R. Salomon ()
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Luc J.W. van der Laan: The Scripps Research Institute Department of Molecular and Experimental Medicine
Christopher Lockey: Genetic Therapy Inc., A Novartis Company
Bradley C. Griffeth: The Scripps Research Institute Department of Molecular and Experimental Medicine
Francine S. Frasier: The Scripps Research Institute Department of Molecular and Experimental Medicine
Carolyn A. Wilson: Food and Drug Administration, Centre for Biologics Evaluation and Research
David E. Onions: University of Glasgow
Bernhard J. Hering: University of Minnesota
Zhifeng Long: Genetic Therapy Inc., A Novartis Company
Edward Otto: Genetic Therapy Inc., A Novartis Company
Bruce E. Torbett: The Scripps Research Institute Department of Molecular and Experimental Medicine
Daniel R. Salomon: The Scripps Research Institute Department of Molecular and Experimental Medicine

Nature, 2000, vol. 407, issue 6800, 90-94

Abstract: 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.

Date: 2000
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DOI: 10.1038/35024089

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