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Chapter 4 : Xenotransplantation

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Abstract:

This chapter reviews the microbiological risks of xenotransplantation as they currently exist, with the caveat that the technical tools of molecular biology are rapidly adding to our knowledge in leaps and bounds. The ethical issue for xenotransplantation from the microbiological aspect is the risk of introducing an unknown infectious agent into a naive human population versus the individual benefit of a life-giving organ transplantation and improved quality of life. There is a large database of information on pigs, from basic anatomy and physiology to specifics of their biochemistry and genome. Production of pigs in barrier facilities operated under very high standards of animal husbandry can consistently yield qualified-pathogen-free animals. The gibbon ape leukemia virus (GALV) behaves as an exogenous retrovirus, but DNA evidence points to the endogenous retrovirus of as the origin. Certainly, the expanding interest in pigs as organ donors has placed the subject of endogenous retroviruses, in particular the porcine endogenous retrovirus (PERV), front and center in the microbiological risk analysis of xenotransplantation. PERV mRNA has been identified at variable levels in all tissues examined, indicating that viral expression is not restricted. Transmission electron microscopy of tissues was negative, although virus-like particles (VLP) were detected in serum. Although the VLP did not bind antibodies against recombinant gag or whole virus, product-enhanced reverse transcriptase analysis produced positive results.

Citation: O'Rourke L. 2000. Xenotransplantation, p 59-84. In Brown C, Bolin C (ed), Emerging Diseases of Animals. ASM Press, Washington, DC. doi: 10.1128/9781555818050.ch4

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Figure 1

phylogenetic tree. An unrooted phylogenetic tree of retroviruses based on alignment of Pol amino acid sequences is shown. The tree was constructed from an alignment of 16 representative retrovirus sequences, corresponding to amino acids 178 to 740 of the predicted PERV-A Pol polyprotein. The values given at the branch forks are the bootstrap percentages for 2,000 samplings, with missing values all being 100%. Sequences were aligned using the CLUSTAL W program, and the PHYLIP package was used for protein distance calculation and tree construction. The solid line below the diagram represents 10% divergence. Diagram courtesy of D. E. Onions, Q-One Biotech, Glasgow, United Kingdom. HSRV, human respiratory syncytial virus; BaEV, baboon endogenous virus; SFV, simian foamy virus; EIAV, equine infectious anemia virus; FIV, feline immunodeficiency virus; RSV, Rous sarcoma virus; MPMV, Mason-Pfizer monkey virus; MMTV, mouse mammary tumor virus; BLV, bovine leukemia virus.

Citation: O'Rourke L. 2000. Xenotransplantation, p 59-84. In Brown C, Bolin C (ed), Emerging Diseases of Animals. ASM Press, Washington, DC. doi: 10.1128/9781555818050.ch4
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