No evidence for productive PERV infection of baboon cells in in vivo infection model.
OBJECTIVE
The discovery that pig endogenous retroviruses are infectious for human cells in vitro lead to vehement discussions about the possible risk of infection after clinical xenotransplantation. Since PERV transmission to non-human primate cells in vitro has been observed, similar to human cells, infection studies in non-human primates should represent the best model to analyze a potential PERV transmission after xenotransplantation. However, it is still open to discussion, whether non-human primate cells can be infected productively-similar to human cells- and whether those species are suitable to analyze PERV infection risks in vivo.


METHODS
In vitro, only few cell types can be tested for susceptibility. We developed a pig to baboon cell transplantation model with special emphasis on B-cell effective immunosuppression, removal of anti Gal-alpha 1,3-Gal-antibodies, inhibition of the complement cascade and long term survival of transplanted cellular grafts. This model allows us to investigate in vivo, whether any baboon cell types may be permissive for productive PERV infection. The xenograft recipients were investigated for up to 535 days post transplantation. Gal-alpha 1,3-Gal-antibody and complement levels were monitored. Potential PERV transmission was analyzed, not only in PBMC, but in a variety of tissue samples as well as in serum and plasma samples by PCR, RT-PCR and by detection of RT-activity. Moreover, potential PERV specific immune responses were studied by a highly sensitive Western-Blot-assay.


RESULTS
Despite several days of extremely low levels of Gal-alpha 1,3-Gal-antibody and complement, and despite of long term xenochimerism, no evidence for PERV infection was obtained in any of the tested tissues or in the tested serum samples.


CONCLUSIONS
This study supplies further evidence for a low susceptibility of baboons towards productive PERV infection after xenotransplantation.
Simon
A R
AR
Leibniz Research Laboratories for Biotechnology and Artificial Organs, Department of Thoracic and Cardiovascular Surgery, Hannover Medical School, Germany.
Templin
C
C
Schröder
C
C
Laaff
G
G
Tessmann
R
R
Winkler
M E
ME
Tacke
S
S
Denner
J
J
Lapin
B
B
Chikobava
M
M
Patience
C
C
Steinhoff
G
G
Agrba
V Z
VZ
Haverich
A
A
Martin
U
U
D000818:Animals; D001483:Base Sequence; D018929:Cell Culture Techniques / Q000379:methods; D017690:Cell Transplantation; D003182:Complement C5 / Q000032:analysis; D017931:DNA Primers; D004187:Disaccharides / Q000032:analysis; D020077:Endogenous Retroviruses / Q000235:genetics / Q000302:isolation & purification*; D007074:Immunoglobulin G / Q000032:analysis; D007150:Immunohistochemistry; D007163:Immunosorbent Techniques; D023421:Models, Animal; D010215:Papio; D016133:Polymerase Chain Reaction / Q000379:methods; D012367:RNA, Viral / Q000302:isolation & purification; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D013552:Swine; D014183:Transplantation, Heterologous / Q000276:immunology
D003182:Complement C5; D017931:DNA Primers; D004187:Disaccharides; D007074:Immunoglobulin G; D012367:RNA, Viral; C055075:galactosyl-(1-3)galactose