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Journal of Virology, December 2001, p. 12252-12265, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12252-12265.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Mapping Full-Length Porcine Endogenous Retroviruses in a Large White Pig

C. Herring,1 G. Quinn,1 R. Bower,1 N. Parsons,1 N. A. Logan,2 A. Brawley,2 K. Elsome,1 A. Whittam,1 X. M. Fernandez-Suarez,1 D. Cunningham,1 D. Onions,2 G. Langford,1 and L. Scobie2,*

Imutran Ltd. (a Novartis Pharma AG Company), Cambridge CB2 2YP,1 and Department of Veterinary Pathology, University of Glasgow, Glasgow G61 1QH,2 United Kingdom

Received 23 July 2001/Accepted 26 September 2001

Xenotransplantation may bridge the widening gap between the shortage of donor organs and the increasing number of patients waiting for transplantation. However, a major safety issue is the potential cross-species transmission of porcine endogenous retroviruses (PERV). This problem could be resolved if it is possible to produce pigs that do not contain replication-competent copies of this virus. In order to determine the feasibility of this, we have determined the number of potentially replication-competent full-length PERV proviruses and obtained data on their integration sites within the porcine genome. We have screened genomic DNA libraries from a Large White pig for potentially intact proviruses. We identified six unique PERV B proviruses that were apparently intact in all three genes, while the majority of isolated proviruses were defective in one or more genes. No intact PERV A proviruses were found in this pig, despite the identification of multiple defective A proviruses. Genotyping of 30 unrelated pigs for these unique proviruses showed a heterogeneous distribution. Two proviruses were uncommon, present in 7 of 30 and 3 of 30 pigs, while three were each present in 24 of 30 pigs, and one was present in 30 of 30 animals examined. Our data indicate that few PERV proviruses in Large White pigs are capable of productive infection and suggest that many could be removed by selective breeding. Further studies are required to determine if all potentially functional proviruses could be removed by breeding or whether gene knockout techniques will be required to remove the residuum.

* Corresponding author. Mailing address: Department of Veterinary Pathology, University of Glasgow, Switchback Rd., Garscube Estate, Glasgow G61 1QH, United Kingdom. Phone: 44 141 330 2283. Fax: 44 141 330 5602. E-mail: l.scobie{at}vet.gla.ac.uk.

Journal of Virology, December 2001, p. 12252-12265, Vol. 75, No. 24
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.24.12252-12265.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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