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(2009)
and prospects for clinical application
Gottlieb (1981)
Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiencyN Engl J Med, 305
G. Scheef, N. Fischer, Ulrich Krach, R. Tönjes (2001)
The Number of a U3 Repeat Box Acting as an Enhancer in Long Terminal Repeats of Polytropic Replication-Competent Porcine Endogenous Retroviruses Dynamically Fluctuates during Serial Virus Passages in Human CellsJournal of Virology, 75
P. Tissier, J. Stoye, Y. Takeuchi, C. Patience, R. Weiss (1997)
Two sets of human-tropic pig retrovirusNature, 389
A. Tucker, C. Belcher, Badru Moloo, J. Bell, T. Mazzulli, A. Humar, A. Hughes, P. McArdle, A. Talbot (2002)
The production of transgenic pigs for potential use in clinical xenotransplantation: microbiological evaluationXenotransplantation, 9
H. Masur, M. Michelis, J. Greene, I. Onorato, R. Stouwe, R. Holzman, G. Wormser, L. Brettman, M. Lange, H. Murray, S. Cunningham‐Rundles (1981)
An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction.The New England journal of medicine, 305 24
D. Kaulitz, Debora Mihica, J. Dorna, Michael Costa, B. Petersen, H. Niemann, R. Tönjes, J. Denner (2011)
Development of sensitive methods for detection of porcine endogenous retrovirus-C (PERV-C) in the genome of pigs.Journal of virological methods, 175 1
J. Denner (1998)
Immunosuppression by Retroviruses: Implications for XenotransplantationAnnals of the New York Academy of Sciences, 862
V. Specke, S. Rubant, J. Denner (2001)
Productive infection of human primary cells and cell lines with porcine endogenous retroviruses.Virology, 285 2
S. Tacke, V. Specke, J. Denner (2003)
Differences in Release and Determination of Subtype of Porcine Endogenous Retroviruses Produced by Stimulated Normal Pig Blood CellsIntervirology, 46
H. Auchincloss, D. Sachs (1998)
Xenogeneic transplantation.Annual review of immunology, 16
M. Uslenghi, Isabella Pagano, C. Pontoni, Salvatore Scuderi, Boris INAFIASF-Milano, INAFCatania Observatory, Inasan, Moscow (2008)
The World Space Observatory (WSO-UV) - Current statusarXiv: Astrophysics
G. Scheef, N. Fischer, E. Flory, I. Schmitt, R. Tönjes (2002)
Transcriptional Regulation of Porcine Endogenous Retroviruses Released from Porcine and Infected Human Cells by Heterotrimeric Protein Complex NF-Y and Impact of Immunosuppressive DrugsJournal of Virology, 76
James Wood, G. Quinn, K. Suling, B. Oldmixon, B. Tine, R. Cina, S. Arn, Christine Huang, L. Scobie, D. Onions, D. Sachs, H. Schuurman, J. Fishman, C. Patience (2004)
Identification of Exogenous Forms of Human-Tropic Porcine Endogenous Retrovirus in Miniature SwineJournal of Virology, 78
U. Martin, M. Winkler, M. Id, H. Radeke, L. Arseniev, Y. Takeuchi, A. Simon, C. Patience, A. Haverich, Prof. Steinhoff (2000)
Productive infection of primary human endothelial cells by pig endogenous retrovirus (PERV)Xenotransplantation, 7
(1998)
Retroviral vectormediated gene transfer into keratocytes in vitro and in vivo
(1999)
Search for crossspecies transmission of porcine endogenous retrovirus in patients treated with living pig tissue
J. Whelan, N. Russell, M. Whelan (2003)
A method for the absolute quantification of cDNA using real-time PCR.Journal of immunological methods, 278 1-2
Ulrich Krach, N. Fischer, Frank Czauderna, R. Kurth, R. Tönjes (2000)
Generation and testing of a highly specific anti‐serum directed against porcine endogenous retrovirus nucleocapsidXenotransplantation, 7
C. Patience, Y. Takeuchi, R. Weiss (1997)
Infection of human cells by an endogenous retrovirus of pigsNature Medicine, 3
V. Specke, V. Specke, S. Tacke, K. Boller, Jochen Schwendemann, J. Denner, J. Denner (2001)
Porcine endogenous retroviruses: in vitro host range and attempts to establish small animal models.The Journal of general virology, 82 Pt 4
C. Rogel-Gaillard, N. Bourgeaux, A. Billault, M. Vaiman, P. Chardon (1999)
Construction of a swine BAC library: application to the characterization and mapping of porcine type C endoviral elementsCytogenetic and Genome Research, 85
R. Pierson, A. Dorling, D. Ayares, M. Rees, J. Seebach, J. Fishman, B. Hering, D. Cooper (2009)
Current status of xenotransplantation and prospects for clinical applicationXenotransplantation, 16
B. Oldmixon, James Wood, T. Ericsson, Carolyn Wilson, M. White-Scharf, G. Andersson, J. Greenstein, H. Schuurman, C. Patience (2002)
Porcine Endogenous Retrovirus Transmission Characteristics of an Inbred Herd of Miniature SwineJournal of Virology, 76
Takele Argaw, A. Ritzhaupt, Carolyn Wilson (2002)
Development of a real time quantitative PCR assay for detection of porcine endogenous retrovirus.Journal of virological methods, 106 1
J. Fishman (1998)
Infection and Xenotransplantation: Developing Strategies to Minimize RiskAnnals of the New York Academy of Sciences, 862
Yong Lee, Sung-Han Park, E. Bae, Y. Jung (2012)
Characterization of molecular clones of porcine endogenous retrovirus-A containing different numbers of U3 repeat boxes in the long terminal repeat region.Journal of virological methods, 181 1
Carolyn Wilson, Susan Wong, M. VanBrocklin, M. Federspiel (2000)
Extended Analysis of the In Vitro Tropism of Porcine Endogenous RetrovirusJournal of Virology, 74
Frank Czauderna, N. Fischer, K. Boller, R. Kurth, R. Tönjes (2000)
Establishment and Characterization of Molecular Clones of Porcine Endogenous Retroviruses Replicating on Human CellsJournal of Virology, 74
B. Åsjö, E. Klein, docent Fenyö, M. Gottlieb, Joel Weisman, P. Fan, Robert Wolf, A. Saxon, L. Morfeldt-Månson, död förintelse, G. Haukenes, L. Haarr, B. Røsok, J. Olofsson, HIVs resa, Kamerun Belgiska, Kongo vagga (1981)
Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency.The New England journal of medicine, 305 24
B. Ekser, M. Ezzelarab, H. Hara, D. Windt, M. Wijkstrom, R. Bottino, M. Trucco, DavidA. Cooper (2012)
Clinical xenotransplantation: the next medical revolution?The Lancet, 379
J. Overbaugh, A. Miller, M. Eiden (2001)
Receptors and Entry Cofactors for Retroviruses Include Single and Multiple Transmembrane-Spanning Proteins as well as Newly Described Glycophosphatidylinositol-Anchored and Secreted ProteinsMicrobiology and Molecular Biology Reviews, 65
Carolyn Wilson, Susan Wong, J. Muller, C. Davidson, T. Rose, P. Burd (1998)
Type C Retrovirus Released from Porcine Primary Peripheral Blood Mononuclear Cells Infects Human CellsJournal of Virology, 72
A. Karlas, M. Irgang, J. Votteler, V. Specke, M. Ozel, R. Kurth, J. Denner (2010)
Characterisation of a human cell-adapted porcine endogenous retrovirus PERV-A/C.Annals of transplantation, 15 2
B. Bartosch, D. Stefanidis, R. Myers, R. Weiss, C. Patience, Y. Takeuchi (2004)
Evidence and Consequence of Porcine Endogenous Retrovirus RecombinationJournal of Virology, 78
Thomas Preuss, N. Fischer, K. Boller, R. Tönjes (2006)
Isolation and Characterization of an Infectious Replication-Competent Molecular Clone of Ecotropic Porcine Endogenous Retrovirus Class CJournal of Virology, 80
J??rgen Blusch, Christian Roos, Hans Nitschko (2000)
A polymerase chain reaction-based protocol for the detection of transmission of pig endogenous retroviruses in pig to human xenotransplantation.Transplantation, 69 10
M. Niebert, R. Tönjes (2003)
Analyses of prevalence and polymorphisms of six replication-competent and chromosomally assigned porcine endogenous retroviruses in individual pigs and pig subspecies.Virology, 313 2
M. Themis, S. Forbes, L. Chan, R. Cooper, C. Etheridge, AD Miller, H. Hodgson, C. Coutelle (1998)
Enhanced in vitro and in vivo gene delivery using cationic agent complexed retrovirus vectorsGene Therapy, 5
Y. Takeuchi, C. Patience, S. Magre, Robin Weiss, Papia Banerjee, P. LeTissier, J. Stoye (1999)
Host range and interference studies of three classes of pig endogenous retrovirus.Journal of virology, 72 12
J. Denner, V. Specke, Ulla Thiesen, A. Karlas, R. Kurth (2003)
Genetic alterations of the long terminal repeat of an ecotropic porcine endogenous retrovirus during passage in human cells.Virology, 314 1
Jungeun Lee, J. Choi, H. Lee, Kang-Chang Kim, Byeong-Sun Choi, Y. Oh, Y. Kim (2011)
Repression of porcine endogenous retrovirus infection by human APOBEC3 proteins.Biochemical and biophysical research communications, 407 1
Z. Pitkin, C. Mullon (1999)
Evidence of absence of porcine endogenous retrovirus (PERV) infection in patients treated with a bioartificial liver support system.Artificial organs, 23 9
Y. Meije, R. Tönjes, J. Fishman (2010)
Retroviral Restriction Factors and Infectious Risk in XenotransplantationAmerican Journal of Transplantation, 10
T. Ericsson, Y. Takeuchi, C. Templin, G. Quinn, S. Farhadian, James Wood, B. Oldmixon, K. Suling, J. Ishii, Y. Kitagawa, T. Miyazawa, D. Salomon, R. Weiss, C. Patience (2003)
Identification of receptors for pig endogenous retrovirusProceedings of the National Academy of Sciences of the United States of America, 100
K. Paradis, G. Langford, Z. Long, W. Heneine, P. Sandstrom, W. Switzer, L. Chapman, Christine Lockey, D. Onions, E. Otto (1999)
Search for cross-species transmission of porcine endogenous retrovirus in patients treated with living pig tissue. The XEN 111 Study Group.Science, 285 5431
B. Seitz, L. Moreira, E. Baktanian, D. Sanchez, B. Gray, E. Gordon, W. Anderson, P. McDonnell (1998)
Retroviral vector-mediated gene transfer into keratocytes in vitro and in vivo.American journal of ophthalmology, 126 5
E. Dörrschuck, N. Fischer, I. Bravo, K. Hanschmann, H. Kuiper, A. Spötter, Ronny Möller, K. Cichutek, C. Münk, R. Tönjes (2011)
Restriction of Porcine Endogenous Retrovirus by Porcine APOBEC3 Cytidine DeaminasesJournal of Virology, 85
Takeuchi (1998)
Host range and interference studies of three classes of pig endogenous retrovirusJ Virol, 72
V. Specke, R. Plesker, James Wood, C. Coulibaly, K. Suling, C. Patience, R. Kurth, H. Schuurman, J. Denner (2009)
No in vivo infection of triple immunosuppressed non‐human primates after inoculation with high titers of porcine endogenous retroviruses *Xenotransplantation, 16
M. Niebert, C. Rogel-Gaillard, P. Chardon, R. Tönjes (2002)
Characterization of Chromosomally Assigned Replication-Competent Gamma Porcine Endogenous Retroviruses Derived from a Large White Pig and Expression in Human CellsJournal of Virology, 76
(2001)
Sensitive and specific immunological detection methods for porcine endogenous retroviruses applicable to experimental and clinical xeno -
Ulrich Krach, N. Fischer, Frank Czauderna, R. Tönjes (2001)
Comparison of Replication-Competent Molecular Clones of Porcine Endogenous Retrovirus Class A and Class B Derived from Pig and Human CellsJournal of Virology, 75
C. Patience, G. Patton, Y. Takeuchi, R. Weiss, M. Mcclure, L. Rydberg, M. Breimer (1998)
No evidence of pig DNA or retroviral infection in patients with short-term extracorporeal connection to pig kidneysThe Lancet, 352
D. Kaulitz, Debora Mihica, R. Plesker, A. Geißler, R. Tönjes, J. Denner (2010)
Absence of infection in pigs inoculated with high-titre recombinant PERV-A/CArchives of Virology, 156
G. Mattiuzzo, S. Ivol, Y. Takeuchi (2009)
Regulation of Porcine Endogenous Retrovirus Release by Porcine and Human TetherinsJournal of Virology, 84
S. Tacke, K. Bodusch, Angelika Berg, J. Denner (2001)
Sensitive and specific immunological detection methods for porcine endogenous retroviruses applicable to experimental and clinical xenotransplantationXenotransplantation, 8
Background Porcine endogenous retroviruses (PERV) pose a zoonotic risk potential in pig‐to‐human xenotransplantation given that PERV capacity to infect different human cell lines in vitro has been clearly shown in the past. However, PERV infectious potential for human peripheral blood mononuclear cells (huPBMC) has been also demonstrated, albeit with controversial results. As productive PERV infection of huPBMC involves immune suppression that may attract opportunistic pathogens as shown for other retroviruses, it is crucial to ascertain unequivocally huPBMC susceptibility for PERV. To address this question, we first investigated in vitro infectivity of PERV for huPBMC using supernatants containing highly infectious PERV‐A/C. Second, huPBMC were cocultivated with PERV‐A/C producer cells to come a step closer to the in vivo situation of xenotransplantation. In addition, cocultivation of huPBMC with porcine PBMC (poPBMC) isolated from German landrace pigs was performed to distinguish PERV replication competence when they were constitutively produced by immortalized cells or by primary poPBMC. Methods Supernatants containing recombinant highly infectious PERV‐A/C were used to infect PHA‐activated huPBMC in the presence or absence of polybrene. Next, PERV‐producing cell lines such as human 293/5° and primary mitogenically activated poPBMC of three German landrace pigs were cocultivated with huPBMC as well as with susceptible human and porcine cell lines as controls. PERV infection was monitored by using three test approaches. The presence of provirus DNA in putatively infected cells was detected via sensitive nested PCR. Viral expression was determined by screening for the activity of gammaretroviral reverse transcriptase (RT) in cell‐free supernatants of infected cells. Virus release was monitored by counting the number of packaged RNA particles in supernatants via PERV‐specific quantitative one‐step real‐time reverse transcriptase PCR. Results Porcine endogenous retroviruses‐A/C in supernatants of human producer 293/5° cells was not able to infect huPBMC. Neither RT activity nor PERV copies were detected. Even provirus could not be detected displaying the inability of PERV‐A/C to induce a productive infection in huPBMC. In cocultivation experiments only non‐productive infection of huPBMC with PERV derived from 293/5° cell line and from PHA‐activated poPBMC was observed by detection of provirus DNA in infected cells. Conclusion Recombinant PERV‐A/C in supernatants of producer cells failed to infect huPBMC, whereas coculture experiments with producer cell lines lead to non‐productive infection of huPBMC. PERV in supernatants seem to have not sufficient infectious potential for huPBMC. However, extensive PERV exposure to huPBMC via cocultivation enabled at least virus cell entry as provirus was detected by nested PCR. Furthermore, results presented support previous data showing German landrace pigs as low producers with negligible infectious potential due to the absence of replication‐competent PERV in the genome. The low PERV expression profile and the lack of significant replication competence of German landrace pigs raise hope for considering these animals as putative donor animals in future pig‐to‐human xenotransplantation. Nonetheless, data imply that PERV still represent a virological risk in the course of xenotransplantation, as the presence of PERV provirus in host cells may lead to a provirus integration resulting in insertional mutagenesis and chromosomal rearrangements.
Xenotransplantation – Wiley
Published: Jan 1, 2014
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