Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice

Animal donors such as pigs could provide an alternative source of organs for transplantation. However, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection 1 , 2 . All pigs contain several copies of porcine endogenous retroviruses (PERV) 3 , 4...

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Veröffentlicht in:Nature (London) 2000-09, Vol.407 (6800), p.90-94
Hauptverfasser: van der Laan, Luc J.W., Lockey, Christopher, Griffeth, Bradley C., Frasier, Francine S., Wilson, Carolyn A., Onions, David E., Hering, Bernhard J., Long, Zhifeng, Otto, Edward, Torbett, Bruce E., Salomon, Daniel R.
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container_issue 6800
container_start_page 90
container_title Nature (London)
container_volume 407
creator van der Laan, Luc J.W.
Lockey, Christopher
Griffeth, Bradley C.
Frasier, Francine S.
Wilson, Carolyn A.
Onions, David E.
Hering, Bernhard J.
Long, Zhifeng
Otto, Edward
Torbett, Bruce E.
Salomon, Daniel R.
description Animal donors such as pigs could provide an alternative source of organs for transplantation. However, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection 1 , 2 . All pigs contain several copies of porcine endogenous retroviruses (PERV) 3 , 4 , and at least three variants of PERV can infect human cell lines in vitro in co-culture, infectivity and pseudotyping experiments 3 , 5 , 6 , 7 . Thus, if xenotransplantation of pig tissues results in PERV viral replication, there is a risk of spreading and adaptation of this retrovirus to the human host. C-type retroviruses related to PERV are associated with malignancies of haematopoietic lineage cells in their natural hosts 8 . Here we show that pig pancreatic islets produce PERV and can infect human cells in culture. After transplantation into NOD/SCID (non-obese diabetic, severe combined immunodeficiency) mice, we detect ongoing viral expression and several tissue compartments become infected. This is the first evidence that PERV is transcriptionally active and infectious cross-species in vivo after transplantation of pig tissues. These results show that a concern for PERV infection risk associated with pig islet xenotransplantation in immunosuppressed human patients may be justified.
doi_str_mv 10.1038/35024089
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(London)</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2000-09-07</date><risdate>2000</risdate><volume>407</volume><issue>6800</issue><spage>90</spage><epage>94</epage><pages>90-94</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><coden>NATUAS</coden><abstract>Animal donors such as pigs could provide an alternative source of organs for transplantation. However, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection 1 , 2 . All pigs contain several copies of porcine endogenous retroviruses (PERV) 3 , 4 , and at least three variants of PERV can infect human cell lines in vitro in co-culture, infectivity and pseudotyping experiments 3 , 5 , 6 , 7 . Thus, if xenotransplantation of pig tissues results in PERV viral replication, there is a risk of spreading and adaptation of this retrovirus to the human host. C-type retroviruses related to PERV are associated with malignancies of haematopoietic lineage cells in their natural hosts 8 . Here we show that pig pancreatic islets produce PERV and can infect human cells in culture. After transplantation into NOD/SCID (non-obese diabetic, severe combined immunodeficiency) mice, we detect ongoing viral expression and several tissue compartments become infected. This is the first evidence that PERV is transcriptionally active and infectious cross-species in vivo after transplantation of pig tissues. These results show that a concern for PERV infection risk associated with pig islet xenotransplantation in immunosuppressed human patients may be justified.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>10993079</pmid><doi>10.1038/35024089</doi><tpages>5</tpages></addata></record>
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subjects Animals
Biological and medical sciences
Cells
Cells, Cultured
Endogenous Retroviruses
Experimental viral diseases and models
Health risks
Hogs
Humanities and Social Sciences
Humans
Infections
Infectious diseases
Islets of Langerhans - virology
letter
Medical sciences
Mice
Mice, Inbred NOD
Mice, SCID
Molecular Sequence Data
multidisciplinary
Pancreas Transplantation - adverse effects
Porcine endogenous retrovirus
Public health
Retroviridae Infections - etiology
Retroviridae Infections - transmission
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - analysis
RNA, Viral - analysis
Rodents
Science
Science (multidisciplinary)
Species Specificity
Swine
Swine - virology
Transplantation
Transplantation Chimera
Transplantation, Heterologous - adverse effects
Viral diseases
Viruses
Xenotransplantation
title Infection by porcine endogenous retrovirus after islet xenotransplantation in SCID mice
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