Porcine endogenous retrovirus released by a bioartificial liver infects primary human cells.
BACKGROUND
Porcine endogenous retrovirus (PERV) remains a safety risk in pig-to-human xenotransplantation. There is no evidence of in vivo productive infection in humans because PERV is inactivated by human serum. However, PERV can infect human cell lines and human primary cells in vitro and inhibit human immune functions.


OBJECTIVE
We investigated the potential of primary porcine liver cells to transmit PERV to primary human cells in a bioreactor-based bioartificial liver (BAL).


METHODS
Primary human hepatocytes, endothelial cells and the human cell line HEK 293 were exposed to supernatants from BAL or from the porcine cell line PK-15. PERV polymerase-specific reverse-transcriptase polymerase chain reaction (RT-PCR) and PCR were used to investigate PERV transmission to human cells. An assay of RT activity was used to detect the presence of retrovirus in the supernatants of BAL, primary human hepatocytes and endothelial cells.


RESULTS
Primary human hepatocytes (hHep), endothelial cells and HEK 293 cells were reproducibly infected by PERV, originating from primary porcine liver cells within the BAL and from PK-15 cells. Infected cells were positive for PERV-specific DNA and RNA after 8-10 days on an average, and RT activity was detectable in the supernatants of infected hHep and HEK 293 cells.


CONCLUSIONS
A risk of PERV infection in human cells is documented in this study, indicating that short-term contact of primary porcine liver cell supernatants with primary human cells could result in PERV transmission.
Frühauf
Jan-Henning
JH
Department of Cell Techniques and Applied Stem Cell Biology, Biomedical-Biotechnological Center (BBZ), Leipzig, Germany.
Mertsching
Heike
H
Giri
Shibashish
S
Frühauf
Nils Roman
NR
Bader
Augustinus
A
D000818:Animals; D002478:Cells, Cultured; D020077:Endogenous Retroviruses / Q000502:physiology*; D042783:Endothelial Cells / Q000821:virology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D019164:Liver, Artificial / Q000821:virology*; D013552:Swine / Q000821:virology*