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Journal of Virology, March 2004, p. 2494-2501, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2494-2501.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Identification of Exogenous Forms of Human-Tropic Porcine Endogenous Retrovirus in Miniature Swine

James C. Wood,1 Gary Quinn,1 Kristen M. Suling,1 Beth A. Oldmixon,1 Brian A. Van Tine,2 Robert Cina,3 Scott Arn,3 Christine A. Huang,3 Linda Scobie,4 David E. Onions,4 David H. Sachs,3 Henk-Jan Schuurman,1 Jay A. Fishman,5 and Clive Patience1*

Immerge BioTherapeutics Inc., Cambridge, Massachusetts 02139,1 Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0005,2 Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129,3 Department of Veterinary Pathology, University of Glasgow, Glasgow G61 1QH, United Kingdom,4 Infectious Disease Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 021145

Received 21 August 2003/ Accepted 29 October 2003

The replication of porcine endogenous retrovirus subgroup A (PERV-A) and PERV-B in certain human cell lines indicates that PERV may pose an infectious risk in clinical xenotransplantation. We have previously reported that human-tropic PERVs isolated from infected human cells following cocultivation with miniature swine peripheral blood mononuclear cells (PBMC) are recombinants of PERV-A with PERV-C. Here, we report that these recombinants are exogenous viruses in miniature swine; i.e., they are not present in the germ line DNA. These viruses were invariably present in miniature swine that transmitted PERV to human cells and were also identified in some miniature swine that lacked this ability. These data, together with the demonstration of the absence of both replication-competent PERV-A and recombinant PERV-A/C loci in the genome of miniature swine (L. Scobie, S. Taylor, J. C. Wood, K. M. Suling, G. Quinn, C. Patience, H.-J. Schuurman, and D. E. Onions, J. Virol. 78:2502-2509, 2004), indicate that exogenous PERV is the principal source of human-tropic virus in these animals. Interestingly, strong expression of PERV-C in PBMC correlated with an ability of the PBMC to transmit PERV-A/C recombinants in vitro, indicating that PERV-C may be an important factor affecting the production of human-tropic PERV. In light of these observations, the safety of clinical xenotransplantation from miniature swine will be most enhanced by the utilization of source animals that do not transmit PERV to either human or porcine cells. Such animals were identified within the miniature swine herd and may further enhance the safety of clinical xenotransplantation.

* Corresponding author. Mailing address: Immerge BioTherapeutics Inc., 300 Technology Sq., Cambridge, MA 02139. Phone: (617) 250-5587. Fax: (617) 241-0539. E-mail: clive.patience{at}immergebt.com.

Journal of Virology, March 2004, p. 2494-2501, Vol. 78, No. 5
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.5.2494-2501.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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