No evidence for productive PERV infection of baboon cells in in vivo infection model.

A. R. Simon, C. Templin, Carsten Schroeder, G. Laaff, R. Tessmann, M. E. Winkler, S. Tacke, J. Denner, B. Lapin, M. Chikobava, C. Patience, G. Steinhoff, V. Z. Agrba, A. Haverich, U. Martin

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

OBJECTIVES: 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. CONCLUSION: This study supplies further evidence for a low susceptibility of baboons towards productive PERV infection after xenotransplantation.

Original languageEnglish (US)
Pages (from-to)24-34
Number of pages11
JournalAnnals of transplantation : quarterly of the Polish Transplantation Society
Volume8
Issue number3
StatePublished - Jan 1 2003
Externally publishedYes

Fingerprint

Papio
Heterologous Transplantation
Infection
Primates
Antibodies
Swine
Endogenous Retroviruses
Polymerase Chain Reaction
Cell Transplantation
Serum
Heterografts
Immunosuppression
B-Lymphocytes
Transplantation
Western Blotting
Transplants
Survival
galactosyl-(1-3)galactose
In Vitro Techniques

ASJC Scopus subject areas

  • Transplantation

Cite this

Simon, A. R., Templin, C., Schroeder, C., Laaff, G., Tessmann, R., Winkler, M. E., ... Martin, U. (2003). No evidence for productive PERV infection of baboon cells in in vivo infection model. Annals of transplantation : quarterly of the Polish Transplantation Society, 8(3), 24-34.

No evidence for productive PERV infection of baboon cells in in vivo infection model. / Simon, A. R.; Templin, C.; Schroeder, Carsten; Laaff, G.; Tessmann, R.; Winkler, M. E.; Tacke, S.; Denner, J.; Lapin, B.; Chikobava, M.; Patience, C.; Steinhoff, G.; Agrba, V. Z.; Haverich, A.; Martin, U.

In: Annals of transplantation : quarterly of the Polish Transplantation Society, Vol. 8, No. 3, 01.01.2003, p. 24-34.

Research output: Contribution to journalArticle

Simon, AR, Templin, C, Schroeder, C, Laaff, G, Tessmann, R, Winkler, ME, Tacke, S, Denner, J, Lapin, B, Chikobava, M, Patience, C, Steinhoff, G, Agrba, VZ, Haverich, A & Martin, U 2003, 'No evidence for productive PERV infection of baboon cells in in vivo infection model.', Annals of transplantation : quarterly of the Polish Transplantation Society, vol. 8, no. 3, pp. 24-34.
Simon, A. R. ; Templin, C. ; Schroeder, Carsten ; Laaff, G. ; Tessmann, R. ; Winkler, M. E. ; Tacke, S. ; Denner, J. ; Lapin, B. ; Chikobava, M. ; Patience, C. ; Steinhoff, G. ; Agrba, V. Z. ; Haverich, A. ; Martin, U. / No evidence for productive PERV infection of baboon cells in in vivo infection model. In: Annals of transplantation : quarterly of the Polish Transplantation Society. 2003 ; Vol. 8, No. 3. pp. 24-34.
@article{5e4c74487b894b0c8428dfcf1ccc9b58,
title = "No evidence for productive PERV infection of baboon cells in in vivo infection model.",
abstract = "OBJECTIVES: 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. CONCLUSION: This study supplies further evidence for a low susceptibility of baboons towards productive PERV infection after xenotransplantation.",
author = "Simon, {A. R.} and C. Templin and Carsten Schroeder and G. Laaff and R. Tessmann and Winkler, {M. E.} and S. Tacke and J. Denner and B. Lapin and M. Chikobava and C. Patience and G. Steinhoff and Agrba, {V. Z.} and A. Haverich and U. Martin",
year = "2003",
month = "1",
day = "1",
language = "English (US)",
volume = "8",
pages = "24--34",
journal = "Annals of Transplantation",
issn = "1425-9524",
publisher = "International Scientific Information, Inc.",
number = "3",

}

TY - JOUR

T1 - No evidence for productive PERV infection of baboon cells in in vivo infection model.

AU - Simon, A. R.

AU - Templin, C.

AU - Schroeder, Carsten

AU - Laaff, G.

AU - Tessmann, R.

AU - Winkler, M. E.

AU - Tacke, S.

AU - Denner, J.

AU - Lapin, B.

AU - Chikobava, M.

AU - Patience, C.

AU - Steinhoff, G.

AU - Agrba, V. Z.

AU - Haverich, A.

AU - Martin, U.

PY - 2003/1/1

Y1 - 2003/1/1

N2 - OBJECTIVES: 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. CONCLUSION: This study supplies further evidence for a low susceptibility of baboons towards productive PERV infection after xenotransplantation.

AB - OBJECTIVES: 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. CONCLUSION: This study supplies further evidence for a low susceptibility of baboons towards productive PERV infection after xenotransplantation.

UR - http://www.scopus.com/inward/record.url?scp=7444253329&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=7444253329&partnerID=8YFLogxK

M3 - Article

C2 - 15114936

AN - SCOPUS:7444253329

VL - 8

SP - 24

EP - 34

JO - Annals of Transplantation

JF - Annals of Transplantation

SN - 1425-9524

IS - 3

ER -