No transmission of porcine endogenous retrovirus in an acute liver failure model treated by a novel hybrid bioartificial liver containing porcine hepatocytes

BACKGROUND： A novel hybrid bioartificial liver（HBAL） was constructed using an anionic resin adsorption column and a multi-layer flat-plate bioreactor containing porcine hepatocytes co-cultured with bone marrow mesenchymal stem cells（MSCs）. This study aimed to evaluate the microbiological safety of the HBAL by detecting the transmission of porcine endogenous retroviruses（PERVs） into canines with acute liver failure（ALF） undergoing HBAL.METHODS： Eight dogs with ALF received a 6-hour HBAL treatment on the first day after the modeling by D-galactosamine administration. The plasma in the HBAL and the whole blood in the dogs were collected for PERV detection at regular intervals until one year later when the dogs were sacrificed to retrieve the tissues of several organs for immunohistochemistry and Western blotting for the investigation of PERV capsid protein gag p30 in the tissue. Furthermore, HEK293 cells were incubated to determine the in vitro infectivity.RESULTS： PERV RNA and reverse transcriptase activity were observed in the plasma of circuit 3, suggesting that PERV particles released in circuit 3. No positive PERV RNA and reverse transcriptase activity were detected in other plasma. No HEK293 cells were infected by the plasma in vitro. In addition, all PERV-related analyses in peripheral blood mononuclear cells and tissues were negative.CONCLUSION： No transmission of PERVs into ALF canines suggested a reliable microbiological safety of HBAL based on porcine hepatocytes.

Ancient origin and complex evolution of porcine endogenous retroviruses

Porcine endogenous retroviruses(PERVs)are proviruses that have medical value in xenotransplantation.However,the evolutionary process leading to the generation of modern PERVs is not well understood.In this study,we in silico mined 14 pig genomes and other available 304 mammalian genomes,which led to the documentation of 185 full-length PERVs or PERV-like sequences.Notably,we found that lesser Egyptian jerboa(Jaculus jaculus),rock hyrax(Procavia capensis)and eight Muridae species all harbored ancestral PERV-like sequences,indicative of ancient cross-species transmission events from none-porcine species to pigs.We also revealed that 11 genomic rearrangement events were mediated via PERVs,during the process of porcine evolution.In conclusion,these new findings help us to understand the complex evolution of the modern PERVs.