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

Denner, Joachim; Laengin, Matthias; Reichart, Bruno; Krueger, Luise; Fiebig, Uwe; Mokelke, Maren; Radan, Julia; Mayr, Tanja; Milusev, Anastasia; Luther, Fabian; Sorvillo, Nicoletta; Rieben, Robert; Brenner, Paolo; Walz, Christoph; Wolf, Eckhard; Roshani, Berit; Stahl–Hennig∥, Christiane; Abicht, Jan‐Michael

doi:10.1101/2020.04.07.029702

Cited by 17 publications

(49 citation statements)

References 64 publications

(57 reference statements)

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“…zoonotic because it has been shown to significantly reduce the survival time of organ xenografts from PCMV/PRVpositive pigs to NHPs. [63][64][65] The pathogenetic mechanism of this virus in the xenosetting is largely unknown, although there is evidence that it promotes cytokine production and leads to a complete loss of the profibrinolytic properties of the endothelial cells. 65 It is also unknown whether PCMV/ PRV can infect human cells.…”

Section: Microbiological Including Virological Safety Requirementsmentioning

confidence: 99%

“…[63][64][65] The pathogenetic mechanism of this virus in the xenosetting is largely unknown, although there is evidence that it promotes cytokine production and leads to a complete loss of the profibrinolytic properties of the endothelial cells. 65 It is also unknown whether PCMV/ PRV can infect human cells. 65 The pathogenic potential of other pig herpesviruses, such as porcine lymphotropic herpesviruses-1, -2, and -3, is still unknown.…”

Section: Microbiological Including Virological Safety Requirementsmentioning

confidence: 99%

“…65 It is also unknown whether PCMV/ PRV can infect human cells. 65 The pathogenic potential of other pig herpesviruses, such as porcine lymphotropic herpesviruses-1, -2, and -3, is still unknown. Of great interest are the ssDNA viruses, which are the most prevalent group identified in virome studies in pigs.…”

Section: Microbiological Including Virological Safety Requirementsmentioning

confidence: 99%

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Pathways to Clinical Cardiac Xenotransplantation

Reichart¹,

Längin

Denner

et al. 2021

Transplantation

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Heart transplantation is the only long-lasting lifesaving option for patients with terminal cardiac failure. The number of available human organs is however far below the actual need, resulting in substantial mortality of patients while waiting for a human heart. Mechanical assist devices are used to support cardiac function but are associated with a high risk of severe complications and poor quality of life for the patients. Consistent success in orthotopic transplantation of genetically modified pig hearts into baboons indicates that cardiac xenotransplantation may become a clinically applicable option for heart failure patients who cannot get a human heart transplant. In this overview, we project potential paths to clinical cardiac xenotransplantation, including the choice of genetically modified source pigs; associated requirements of microbiological, including virological, safety; optimized matching of source pig and recipient; and specific treatments of the donor heart after explantation and of the recipients. Moreover, selection of patients and the regulatory framework will be discussed.

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Section: Microbiological Including Virological Safety Requirementsmentioning

confidence: 99%

Section: Microbiological Including Virological Safety Requirementsmentioning

confidence: 99%

Section: Microbiological Including Virological Safety Requirementsmentioning

confidence: 99%

See 1 more Smart Citation

Pathways to Clinical Cardiac Xenotransplantation

Reichart¹,

Längin

Denner

et al. 2021

Transplantation

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“…Since the survival time of the transplant with the higher virus load was longer, the effect seems to be low. On the other hand, animals D and E were also infected with PCMV in addition to PCV3 [40]. It is well known that PCMV significantly reduces the survival time of pig kidney and heart transplants in non-human primates [41].…”

Section: Discussionmentioning

confidence: 99%

Transmission of Porcine Circovirus 3 (PCV3) by Xenotransplantation of Pig Hearts into Baboons

Krüger

Längin

Reichart

et al. 2019

Viruses

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Porcine circovirus 3 (PCV3) is a newly described member of the virus family Circoviridae. PCV3 is highly distributed among pigs and wild boars worldwide. A sudden introduction of PCV3 was recently observed in a herd of triple genetically modified pigs generated for xenotransplantation. These animals were used as donor pigs for orthotopic heart transplantation into baboons. In four cases, PCV3-positive hearts were transplanted, and transmission of PCV3 to the recipient was observed. PCV3 was found in all organs of the recipient baboons and a higher virus load was found in animals with a longer survival time of the transplant, indicating replication of the virus. This is the first report showing trans-species transmission of PCV3 to baboons by transplantation of a heart from a PCV3-positive donor pig. Sequence analysis showed that PCV3a and PCV3b were present in the infected pigs and were transmitted. Experiments to infect human 293 cells with PCV3 failed.

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“…It can be transmitted to humans by undercooked pork or contact with pigs, 23 and transmission from human to human by blood transfusion was reported. 26 PCMV at least is responsible for a shorter survival time of pig transplants in non-human primates, 21,22,27,28,29 . PERVs, although not yet transmitted in preclinical and clinical trials, are suspected (as all retroviruses) to induce immunodeficiency and tumors.…”

Section: Introductionmentioning

confidence: 99%