Impact of porcine cytomegalovirus on long-term orthotopic cardiac xenotransplant survival

被引：75

作者：

Denner, Joachim ^{[1
]}

Langin, Matthias ^{[2
,3
]}

Reichart, Bruno ^{[3
]}

Kruger, Luise ^{[1
]}

Fiebig, Uwe ^{[1
]}

Mokelke, Maren ^{[3
]}

Radan, Julia ^{[3
]}

Mayr, Tanja ^{[2
]}

Milusev, Anastasia ^{[4
]}

Luther, Fabian ^{[4
]}

Sorvillo, Nicoletta ^{[4
]}

Rieben, Robert ^{[4
]}

Brenner, Paolo ^{[5
]}

Walz, Christoph ^{[6
]}

Wolf, Eckhard ^{[7
,8
]}

Roshani, Berit ^{[9
]}

Stahl-Hennig, Christiane ^{[9
]}

Abicht, Jan-Michael ^{[2
,3
]}

机构：

[1] Robert Koch Inst, Berlin, Germany

[2] Ludwig Maximilians Univ Munchen, Univ Hosp, Dept Anaesthesiol, Munich, Germany

[3] Ludwig Maximilians Univ Munchen, Walter Brendel Ctr Expt Med, Munich, Germany

[4] Univ Bern, Dept Biomed Res DMBR, Bern, Switzerland

[5] Maximilians Univ Munchen, Univ Hosp, Dept Cardiac Surg, Munich, Germany

[6] Ludwig Maximilians Univ Munchen, Fac Med, Inst Pathol, Munich, Germany

[7] Ludwig Maximilians Univ Munchen, Gene Ctr, Anim Breeding & Biotechnol, Munich, Germany

[8] Ludwig Maximilians Univ Munchen, Dept Vet Sci, Munich, Germany

[9] German Primate Ctr, Unit Infect Models, Gottingen, Germany

来源：

SCIENTIFIC REPORTS | 2020年 / 10卷 / 01期

关键词：

HEMATOPOIETIC-CELL TRANSPLANTATION; DELAYED XENOGRAFT REJECTION; ENDOGENOUS RETROVIRUS; LYMPHOPROLIFERATIVE DISEASE; LYMPHOTROPIC HERPESVIRUS; SYSTEMIC INFLAMMATION; HEART REGENERATION; PIG; ACTIVATION; COAGULATION;

D O I：

10.1038/s41598-020-73150-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Xenotransplantation using pig organs has achieved survival times up to 195 days in pig orthotopic heart transplantation into baboons. Here we demonstrate that in addition to an improved immunosuppressive regimen, non-ischaemic preservation with continuous perfusion and control of post-transplantation growth of the transplant, prevention of transmission of the porcine cytomegalovirus (PCMV) plays an important role in achieving long survival times. For the first time we demonstrate that PCMV transmission in orthotopic pig heart xenotransplantation was associated with a reduced survival time of the transplant and increased levels of IL-6 and TNF alpha were found in the transplanted baboon. Furthermore, high levels of tPA-PAI-1 complexes were found, suggesting a complete loss of the pro-fibrinolytic properties of the endothelial cells. These data show that PCMV has an important impact on transplant survival and call for elimination of PCMV from donor pigs.

引用

页数：14

共 86 条

[41] A broadly reactive one-step real-time RT-PCR assay for rapid and sensitive detection of hepatitis E virus [J].

Jothikumar, N ;

Cromeans, TL ;

Robertson, BH ;

Meng, XJ ;

Hill, VR .

JOURNAL OF VIROLOGICAL METHODS, 2006, 131 (01) :65-71

[42] Development of sensitive methods for detection of porcine endogenous retrovirus-C (PERV-C) in the genome of pigs [J].

Kaulitz, Danny ;

Mihica, Debora ;

Dorna, Jens ;

Costa, Michael Rodrigues ;

Petersen, Bjorn ;

Niemann, Heiner ;

Toenjes, Ralf R. ;

Denner, Joachim .

JOURNAL OF VIROLOGICAL METHODS, 2011, 175 (01) :60-65

[43] Generation of neutralising antibodies against porcine endogenous retroviruses (PERVs) [J].

Kaulitz, Danny ;

Fiebig, Uwe ;

Eschricht, Magdalena ;

Wurzbacher, Christian ;

Kurth, Reinhard ;

Denner, Joachim .

VIROLOGY, 2011, 411 (01) :78-86

[44] Application of the Multiplex Cytokine Analysis to Monitor Xenogeneic Immune Responses to the Porcine Islet Graft in Non-Human Primate [J].

Kim, Yong-Hee ;

Kim, Jung-Sik ;

Yoon, Il-Hee ;

Shin, Jun-Seop ;

Kim, Jong-Min ;

Kim, Sang-Joon ;

Park, Chung-Gyu .

JOURNAL OF KOREAN MEDICAL SCIENCE, 2013, 28 (12) :1729-1733

[45] Microbial translocation, immune activation, and HIV disease [J].

Klatt, Nichole R. ;

Funderburg, Nicholas T. ;

Brenchley, Jason M. .

TRENDS IN MICROBIOLOGY, 2013, 21 (01) :6-13

[46] Current Knowledge on Porcine circovirus 3 (PCV-3): A Novel Virus With a Yet Unknown Impact on the Swine Industry [J].

Klaumann, Francini ;

Correa-Fiz, Florencia ;

Franzo, Giovanni ;

Sibila, Marina ;

Nunez, Jose I. ;

Segales, Joaquim .

FRONTIERS IN VETERINARY SCIENCE, 2018, 5

[47] Human herpesvirus 6 and multiple sclerosis: Systemic active infections in patients with early disease [J].

Knox, KK ;

Brewer, JH ;

Henry, JM ;

Harrington, DJ ;

Carrigan, DR .

CLINICAL INFECTIOUS DISEASES, 2000, 31 (04) :894-903

[48] Transmission of Porcine Circovirus 3 (PCV3) by Xenotransplantation of Pig Hearts into Baboons [J].

Krueger, Luise ;

Laengin, Matthias ;

Reichart, Bruno ;

Fiebig, Uwe ;

Kristiansen, Yannick ;

Prinz, Carolin ;

Kessler, Barbara ;

Egerer, Stefanie ;

Wolf, Eckhard ;

Abicht, Jan-Michael ;

Denner, Joachim .

VIRUSES-BASEL, 2019, 11 (07)

[49] Consistent success in life-supporting porcine cardiac xenotransplantation [J].

Laengin, Matthias ;

Mayr, Tanja ;

Reichart, Bruno ;

Michel, Sebastian ;

Buchholz, Stefan ;

Guethoff, Sonja ;

Dashkevich, Alexey ;

Baehr, Andrea ;

Egerer, Stefanie ;

Bauer, Andreas ;

Mihalj, Maks ;

Panelli, Alessandro ;

Issl, Lara ;

Ying, Jiawei ;

Fresch, Ann Kathrin ;

Buttgereit, Ines ;

Mokelke, Maren ;

Radan, Julia ;

Werner, Fabian ;

Lutzmann, Isabelle ;

Steen, Stig ;

Sjoberg, Trygve ;

Paskevicius, Audrius ;

Liao Qiuming ;

Sfriso, Riccardo ;

Rieben, Robert ;

Dahlhoff, Maik ;

Kessler, Barbara ;

Kemter, Elisabeth ;

Klett, Katharina ;

Hinkel, Rabea ;

Kupatt, Christian ;

Falkenau, Almuth ;

Reu, Simone ;

Ellgass, Reinhard ;

Herzog, Rudolf ;

Binder, Uli ;

Wich, Guenter ;

Skerra, Arne ;

Ayares, David ;

Kind, Alexander ;

Schoenmann, Uwe ;

Kaup, Franz-Josef ;

Hagl, Christian ;

Wolf, Eckhard ;

Klymiuk, Nikolai ;

Brenner, Paolo ;

Abicht, Jan-Michael .

NATURE, 2018, 564 (7736) :430-+

[50] Specific ablation of CD4+ T-cells promotes heart regeneration in juvenile mice [J].

Li, Jiatao ;

Liang, Cai ;

Yang, Kevin Y. ;

Huang, Xiuzhen ;

Han, Mao Ying ;

Li, Xisheng ;

Chan, Vicken W. ;

Chan, Kathleen S. ;

Liu, Di ;

Huang, Zhan-Peng ;

Zhou, Bin ;

Lui, Kathy O. .

THERANOSTICS, 2020, 10 (18) :8018-8035

← 1 2 3 4 5 6 7 8 9 →