One of the important barriers to xenotransplantation is the possibility of transmission of zoonotic disease to human recipients. Microbiological safety must be assured before clinical applications can be realized.

The use of organs across the species barrier may be associated with the risk of transmission of microorganisms, especially porcine endogenous retroviruses (PERVs), which are an integral part of the porcine genome and infect human cells in vitro[1]. It is still unknown whether PERVs can infect human transplant recipients in vivo and, if so, whether they are pathogenic[2]. In first clinical xenotransplantation trials human patients who were treated with pig cells did not develop antibodies against PERV or show provirus integration[3], indicating that no virus infection had taken place.

Many of the more than 50 proviral copies located in the pig genome are unable to produce infectious virus due to deletions and mutations. Such defective viruses have been found in many other species, including man[6]. However, infectious particles may be produced not only by replication-competent viruses, but also as the result of recombination and/or complementation of intact genes from defective proviruses[6].

There are several possible approaches to preventing PERV transmission to the transplant recipient.

Second, it may be possible to develop a vaccine against PERV. While vaccines against retroviruses like HIV have not been successful, vaccines against type C retroviruses such as MuLV and FeLV, exist [7].

While approaches to preventing PERV transmission are being developed, monitoring is available.

In short, cross-species transmission and recombination of retroviruses could pose a significant threat to public, as well as graft recipient health. While the level of risk is unknown, it cannot be dismissed, especially since xenotransplantation recipients will certainly be treated with heavy immunosuppression.

References

1. Patience, C., Switzer, W., Takeuchi, Y., Griffiths, D., Goward, M., Heneine, W., Stoye, J. and Weiss, R., 2001. Multiple groups of novel retroviral genomes in pigs and related species. J. Virol. 75 6, pp. 2771–2775.
2. Denner, J., 1987. Immunosuppression by oncogenic retroviridae. In: Zschiesche, W., Editor, , 1987. Modulation of the Immune Responsiveness by Infectious Agents, Fischer Verlag, Jena, pp. 140–201
3. Paradis, K., Langford, G., Long, Z., Heneine, W., Sandstrom, P., Switzer, W., Chapman, L., Lockey, C., Onions, D. and Otto, E., 1999. Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group. Science 285 543, pp. 1236–1241.
4. Oldmixon, B.A., Wood, J.C., Ericsson, T.A., Wilson, C.A., White-Scharf, M.E., Andersson, G., Greenstein, J.L., Schuurman, H.J. and Patience, C., 2002. Porcine endogenous retrovirus transmission characteristics of an inbred herd of miniature swine. J. Virol. 76 6, pp. 3045–3048.
5. Dai, Y., Vaught, T.D., Boone, J., Chen, S.H., Phelps, C.J., Ball, S., Monahan, J.A., Jobst, P.M., McCreath, K.J., Lamborn, A.E., Cowell-Lucero, J.L., Wells, K.D., Colman, A., Polejaeva, I.A. and Ayares, D.L., 2002. Targeted disruption of the alpha1,3-galactosyltransferase gene in cloned pigs. Nat. Biotechnol. 20 3, pp. 251–255.
6. Löwer, R., Löwer, J. and Kurth, R., 1996. The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proc. Natl. Acad. Sci. USA 93 11, pp. 5177–5184.
7. Lee, J., Ihle, J. and Huebner, R., 1977. The humoral immune response of NIH Swiss and SWR/J mice to vaccination with formalinized AKR or Gross murine leukemia virus. Proc. Natl. Acad. Sci. USA 74 1, pp. 343–347.
8. Takele Argaw, Armin Ritzhaupt and Carolyn A. Wilson, 2002. Development of a real time quantitative PCR assay for detection of porcine endogenous retrovirus Journal of Virological Methods. Volume 106, Issue 1 , October 2002, Pages 97-106