Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs
Abstract Background Porcine endogenous retroviruses (PERVs) can infect human cells and pose a risk for xenotransplantation when pig cells, tissues or organs are transplanted to human recipients. Xenotransplantation holds great promise to overcome the shortage of human donor organs after solving the...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-02-01
|
| Series: | Virology Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12985-022-01742-0 |
| _version_ | 1818982099663716352 |
|---|---|
| author | Sabrina Halecker Ludwig Krabben Yannick Kristiansen Luise Krüger Lars Möller Dietmar Becher Michael Laue Benedikt Kaufer Christian Reimer Joachim Denner |
| author_facet | Sabrina Halecker Ludwig Krabben Yannick Kristiansen Luise Krüger Lars Möller Dietmar Becher Michael Laue Benedikt Kaufer Christian Reimer Joachim Denner |
| author_sort | Sabrina Halecker |
| collection | DOAJ |
| description | Abstract Background Porcine endogenous retroviruses (PERVs) can infect human cells and pose a risk for xenotransplantation when pig cells, tissues or organs are transplanted to human recipients. Xenotransplantation holds great promise to overcome the shortage of human donor organs after solving the problems of rejection, functionality and virus safety. We recently described the transmission of a human-tropic recombinant PERV-A/C, designated PERV-F, from peripheral blood mononuclear cells (PBMCs) of a Göttingen Minipig (GöMP) to human 293 cells (Krüger et al., in Viruses 12(1):38, 2019). The goal of this study was to characterize PERV-F in more detail and to analyze the probability of virus isolation from other animals. Methods The recombination site in the envelope (env) gene, the long terminal repeats (LTR), the proteins and the morphology of the recombinant PERV-F were characterized by polymerase chain reaction (PCR), sequencing, Western blot analysis, immunofluorescence, and transmissible electron microscopy. Mitogen-stimulated PBMCs from 47 additional pigs, including 17 new GöMP, were co-cultured with highly susceptible human 293 T cells, and the PERV-A/C prevalence and PERV transmission was analyzed by PCR. Results PERV-F, isolated from a GöMP, is an infectious human-tropic PERV-A/C virus with a novel type of recombination in the env gene. The length of the LTR of PERV-F increased after passaging on human cells. In a few minipigs, but not in German landrace pigs, PERV-A/C were found. There was no transmission of human-tropic PERV-A/C from additional 47 pigs, including 17 GöMP, to human cells. Conclusion These data show that human-tropic recombinant PERV-A/C proviruses can only be found in a very small number of minipigs, but not in other pigs, and that their isolation as infectious virus able to replicate on human cells is an extremely rare event, even when using highly susceptible 293 cells. |
| first_indexed | 2024-12-20T17:41:50Z |
| format | Article |
| id | doaj.art-2a398a1708a44e19ba2ab5553c9c84a4 |
| institution | Directory Open Access Journal |
| issn | 1743-422X |
| language | English |
| last_indexed | 2024-12-20T17:41:50Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Virology Journal |
| spelling | doaj.art-2a398a1708a44e19ba2ab5553c9c84a42022-12-21T19:31:05ZengBMCVirology Journal1743-422X2022-02-0119111310.1186/s12985-022-01742-0Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigsSabrina Halecker0Ludwig Krabben1Yannick Kristiansen2Luise Krüger3Lars Möller4Dietmar Becher5Michael Laue6Benedikt Kaufer7Christian Reimer8Joachim Denner9Institute of Virology, Free University BerlinInstitute of Virology, Free University BerlinRobert Koch InstituteRobert Koch InstituteCentre for Biological Threats and Special Pathogens ZBS 4: Advanced Light and Electron Microscopy, Robert Koch InstituteMICROMUN, Privates Institut Für Mikrobiologische Forschung GmbHCentre for Biological Threats and Special Pathogens ZBS 4: Advanced Light and Electron Microscopy, Robert Koch InstituteInstitute of Virology, Free University BerlinDepartment of Animal Sciences, Animal Breeding and Genetics Group, University of GöttingenInstitute of Virology, Free University BerlinAbstract Background Porcine endogenous retroviruses (PERVs) can infect human cells and pose a risk for xenotransplantation when pig cells, tissues or organs are transplanted to human recipients. Xenotransplantation holds great promise to overcome the shortage of human donor organs after solving the problems of rejection, functionality and virus safety. We recently described the transmission of a human-tropic recombinant PERV-A/C, designated PERV-F, from peripheral blood mononuclear cells (PBMCs) of a Göttingen Minipig (GöMP) to human 293 cells (Krüger et al., in Viruses 12(1):38, 2019). The goal of this study was to characterize PERV-F in more detail and to analyze the probability of virus isolation from other animals. Methods The recombination site in the envelope (env) gene, the long terminal repeats (LTR), the proteins and the morphology of the recombinant PERV-F were characterized by polymerase chain reaction (PCR), sequencing, Western blot analysis, immunofluorescence, and transmissible electron microscopy. Mitogen-stimulated PBMCs from 47 additional pigs, including 17 new GöMP, were co-cultured with highly susceptible human 293 T cells, and the PERV-A/C prevalence and PERV transmission was analyzed by PCR. Results PERV-F, isolated from a GöMP, is an infectious human-tropic PERV-A/C virus with a novel type of recombination in the env gene. The length of the LTR of PERV-F increased after passaging on human cells. In a few minipigs, but not in German landrace pigs, PERV-A/C were found. There was no transmission of human-tropic PERV-A/C from additional 47 pigs, including 17 GöMP, to human cells. Conclusion These data show that human-tropic recombinant PERV-A/C proviruses can only be found in a very small number of minipigs, but not in other pigs, and that their isolation as infectious virus able to replicate on human cells is an extremely rare event, even when using highly susceptible 293 cells.https://doi.org/10.1186/s12985-022-01742-0XenotransplantationPorcine endogenous retrovirusesRecombinationLong terminal repeatsCopy number |
| spellingShingle | Sabrina Halecker Ludwig Krabben Yannick Kristiansen Luise Krüger Lars Möller Dietmar Becher Michael Laue Benedikt Kaufer Christian Reimer Joachim Denner Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs Virology Journal Xenotransplantation Porcine endogenous retroviruses Recombination Long terminal repeats Copy number |
| title | Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs |
| title_full | Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs |
| title_fullStr | Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs |
| title_full_unstemmed | Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs |
| title_short | Rare isolation of human-tropic recombinant porcine endogenous retroviruses PERV-A/C from Göttingen minipigs |
| title_sort | rare isolation of human tropic recombinant porcine endogenous retroviruses perv a c from gottingen minipigs |
| topic | Xenotransplantation Porcine endogenous retroviruses Recombination Long terminal repeats Copy number |
| url | https://doi.org/10.1186/s12985-022-01742-0 |
| work_keys_str_mv | AT sabrinahalecker rareisolationofhumantropicrecombinantporcineendogenousretrovirusespervacfromgottingenminipigs AT ludwigkrabben rareisolationofhumantropicrecombinantporcineendogenousretrovirusespervacfromgottingenminipigs AT yannickkristiansen rareisolationofhumantropicrecombinantporcineendogenousretrovirusespervacfromgottingenminipigs AT luisekruger rareisolationofhumantropicrecombinantporcineendogenousretrovirusespervacfromgottingenminipigs AT larsmoller rareisolationofhumantropicrecombinantporcineendogenousretrovirusespervacfromgottingenminipigs AT dietmarbecher rareisolationofhumantropicrecombinantporcineendogenousretrovirusespervacfromgottingenminipigs AT michaellaue rareisolationofhumantropicrecombinantporcineendogenousretrovirusespervacfromgottingenminipigs AT benediktkaufer rareisolationofhumantropicrecombinantporcineendogenousretrovirusespervacfromgottingenminipigs AT christianreimer rareisolationofhumantropicrecombinantporcineendogenousretrovirusespervacfromgottingenminipigs AT joachimdenner rareisolationofhumantropicrecombinantporcineendogenousretrovirusespervacfromgottingenminipigs |