183

The hepatitis E virus does not appear to be transmitted via xenotransplantation

Linda Scobie¹, Claire Crossan¹, Stacey Busby¹, M Matouskova², Jiri Hejnar², Josef Blaha², Pavel Vesely², Bjoern Petersen⁴, Yasu Takeuchi³

¹Biological and Biomedical Science, Glasgow Caledonian University, Glasgow, United Kingdom; ²Department of Cellular and Viral Genetics, Institute of Molecular Genetics, Prague, Czech Republic; ³Division of Infection and Immunity, University College London, London, United Kingdom; ⁴Department of Biotechnology, Friedrich-Loeffler-Institut, Neustadt a.Rbge, Germany

Hepatitis E (HEV) is an emerging virus of concern to xenotransplantation. It is predominately transmitted via the faecal oral route and it is endemic in countries with poor sanitation. Previously it was only thought to cause acute hepatitis but has recently been seen to cause a chronic hepatitis leading to cirrhosis in liver, kidney and pancreas in allo-transplant patients. In addition, pigs have been implicated as a source of zoonotic transmission and as HEV can be transmitted via blood transfusion and transplantation, it is of great concern for xenotransplantation (Xtn).

Methods: Donor animals from herds used for porcine xenografts were assessed for the prevalence of HEV and non-human primates (NHPs) receiving xenografts were also assessed for their HEV status pre and post Xtn. In addition, individuals who had received porcine skin xenografts were tested for HEV sero-prevalence in comparison to a control population.

Results and Conclusion: Pigs from commercial, barrier house and SPF facilities were tested and 70%, 58% and 33% pigs were found to be sero-positive for HEV respectively. HEV screening on xenografted individuals demonstrated no significant difference (p=0.684) between those receiving a xenograft (n=40) and those of the normal control population (n=34). Finally, HEV was identified in a number of xenografted NHPs; the virus was amplified and sequenced from donor animals and NHPs to confirm if HEV present was derived from a pig or primate source. Extensive sequencing of HEV amplicons in two regions from both pig and NHP recipients has shown that there appears to be a reactivation of primate HEV in NHPs receiving xenografts. There was no published data for primate HEV previously, however, from phylogenetic analysis, the virus present does not appear to be of pig origin and the biological consequences of HEV reactivation are being further investigated.

This work was supported by the European Commission’s Sixth Framework Programme contract no. LSHB-CT-2006-037377, XENOME