2013 - IXA 2013 Congress
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Luncheon Seminar: Zoonosis/ Regulation
39.2 - PERVs in Xenotransplantation
Presenter: Yasuhiro, Takeuchi, Baltimore, United Kingdom
Authors:
PERVs in xenotransplantation
Yasuhiro Takeuchi
Division of Infection and Immunity, UCL, London, UK.
Zoonotic transmission via xenotransplantation and further spread to the public of porcine endogenous retroviruses (PERVs) remains a theoretical, potential risk. Accordingly, precautionary approaches in control of PERV in the source animals and post-transplantation PERV monitoring in patients continue to be of paramount importance (1).
With regard to the source animal, a high-quality, swine whole genome sequence (SWGS) derived from a single Duroc sow was published recently (2). This confirmed earlier indications that: 1) introduction of PERV into the pig genome is relatively recent and integration sites are highly polymorphic; 2) only a limited number of PERV loci are active and can direct production of infectious viruses; indeed no ‘intact’ PERV sequence was found in the SWGS. Therefore, detailed genomic analyses of source animals may help selection of pigs with low or negligible PERV infectivity. This SWGS can serve as the template for re-sequencing of candidate source animals in future.
Retrospective PERV testings of xenograft recipients continues including investigating the long-term effects (3). As virus detection sensitivity increases, there may be a lesson to be learned from recent false positive virus detection outside the xenotransplantation field: XMRV (xenotropic murine leukemia virus-related virus), a close relative of PERV within the genus of gammaretrovirus, had been falsely associated with both prostate cancer and chronic fatigue syndrome. Alarmingly XMRV originated in human-to-mouse experimental xenotransplantation where the graft (human prostate cancer cells) picked up the host endogenous virus (murine leukemia virus) (4). Caution in interpreting true or false PERV infection should continue to be a consideration in PERV monitoring.
(1) Fishman, J. A., L. Scobie, and Y. Takeuchi. 2012. Xenotransplantation-associated infectious risk: a WHO consultation. Xenotransplantation 19: 72-81.
(2) Groenen, M. A., et al. 2012. Analyses of pig genomes provide insight into porcine demography and evolution. Nature 491: 393-398.
(3) Scobie, L. et al. 2013 Long-term IgG response to porcine Neu5Gc-antigens without transmission of PERV in burn patients treated with porcine skin xenografts. J Immunol. in press
(4) Paprotka T, et al. Recombinant origin of the retrovirus XMRV. 2011. Science. 333:97-101
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