Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice

Rcjohnsen rcjohnsen at aol.com
Mon Sep 11 19:05:26 EST 2000


Nature 407, 90 - 94 (2000) © Macmillan Publishers Ltd. 
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* & DANIEL R. SALOMON* 
* 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 and requests for materials should be addressed to: D.R.S.
(email: dsalomon at 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, 5-7. 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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