Expression of pig endogenous retrovirus by primary porcine endothelial cells and infection of human cells.
BACKGROUND
The risk of interspecies transmission of retroviruses during xenotransplantation is suggested by reports of pig endogenous retrovirus (PERV) released from porcine cell lines productively infecting human cell lines in vitro and of infectious PERV being released from pig peripheral blood mononuclear cells after mitogenic stimulation. Endothelial cells are the main interface between a xenograft and the recipient's leucocytes and tissues.


METHODS
We have analysed pig primary aortic endothelial cells (PAEC) together with other transplantation-relevant porcine cells and tissues for expression of PERV mRNA. Release of virus particles by PAEC was monitored by reverse transcriptase (RT) activity in the medium of cultured PAEC. Infectivity for human cells was tested by co-cultivation of irradiated PAEC with the human embryonal kidney cell line HEK293 and looking for virus release from the human cells.


RESULTS
PAECs, hepatocytes, lung, and skin from a variety of pig strains and breeds expressed PERV mRNA. PAEC released infectious particles. Co-cultivation of PAEC and HEK293 led to productive infection of the human cells and expression of PERV types A and B.


CONCLUSIONS
Release of infectious virus from PAEC occurred without mitogenic stimulation, suggesting a serious risk of retrovirus transfer after xenotransplantation.
Martin
U
U
Leibniz Research Laboratories for Biotechnology and Artificial Organs, Hannover Medical School, Germany. umartin@artificial-organs.de
Kiessig
V
V
Blusch
J H
JH
Haverich
A
A
von der Helm
K
K
Herden
T
T
Steinhoff
G
G
D000818:Animals; D002478:Cells, Cultured / Q000821:virology*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000821:virology*; D006801:Humans; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D012190:Retroviridae / Q000235:genetics / Q000302:isolation & purification*; D012192:Retroviridae Infections / Q000635:transmission*; D017422:Sequence Analysis, DNA; D013552:Swine; D014183:Transplantation, Heterologous
D012333:RNA, Messenger; D012367:RNA, Viral