Porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV): A threat for xenotransplantation?

Mueller, Nicolas J.; Denner, Joachim

doi:10.1111/xen.12775

Cited by 19 publications

(21 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cells harboring the latent virus are everywhere: in the case of stress or in the absence of the control by the immune system, the virus starts to replicate again, resulting in a high virus load in the circulation. In the transplant setting the virus replicates unhindered in the transplant and interacts with immune and endothelial cells of the recipient, causing a multi‐organ failure 51 . Infection of pigs usually occurs early in life and mainly from mothers to piglets 57 .…”

Section: The Role Of Pcmvmentioning

confidence: 99%

“…For a correct understanding, we present a short summary of the virus. 50,51 PCMV is a pig betaherpesvirus with a misleading name.…”

Section: The Role Of Pcmvmentioning

confidence: 99%

“…In the transplant setting the virus replicates unhindered in the transplant and interacts with immune and endothelial cells of the recipient, causing a multi-organ failure. 51 Infection of pigs usually occurs early in life and mainly from mothers to piglets. 57 It is still unclear whether or not PCMV can infect human cells 58,59 -by recent evidence not-and whether it can adapt to another species as many other herpesviruses can.…”

Section: The Role Of Pcmvmentioning

confidence: 99%

“…In conclusion, the POC studies summarized in this report bring xenotransplantation a step further to clinical application: most important, the data do not block but facilitate the next phase. A major lesson learned from the study at UMD is that virus safety is pivotal for the success of xenotransplantation 1,51 and that testing should be done with assays of the highest quality and following an optimal strategy in the animal testing protocol. [63][64][65][66] There are still hurdles to overcome before a porcine solid organ xenotransplantation product will enter clinical medicine.…”

Section: Interpretation and Conclusionmentioning

confidence: 99%

See 3 more Smart Citations

Early testing of porcine organ xenotransplantation products in humans: Microbial safety as illustrated for porcine cytomegalovirus

Denner

Schuurman²

2022

Xenotransplantation

Self Cite

View full text Add to dashboard Cite

Section: The Role Of Pcmvmentioning

confidence: 99%

“…For a correct understanding, we present a short summary of the virus. 50,51 PCMV is a pig betaherpesvirus with a misleading name.…”

Section: The Role Of Pcmvmentioning

confidence: 99%

Section: The Role Of Pcmvmentioning

confidence: 99%

Section: Interpretation and Conclusionmentioning

confidence: 99%

See 2 more Smart Citations

Early testing of porcine organ xenotransplantation products in humans: Microbial safety as illustrated for porcine cytomegalovirus

Denner

Schuurman²

2022

Xenotransplantation

Self Cite

View full text Add to dashboard Cite

“…Like all herpes viruses, PCMV/PRV is able to establish latency, which makes it difficult to detect the virus. During latency the viral DNA is stably maintained in the nucleus of the infected cells and the protein expression in latently infected cells is decreased 27 , 28 . In this situation, highly sensitive detection methods are needed and the knowledge what and how to test.…”

Section: Introductionmentioning

confidence: 99%

How, where and when to screen for porcine cytomegalovirus (PCMV) in donor pigs for xenotransplantation

Halecker

Hansen

Krabben

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Porcine cytomegalovirus (PCMV), that is actually a porcine roseolovirus (PRV), is a common herpesvirus in domestic pigs and wild boars. In xenotransplantation, PCMV/PRV has been shown to significantly reduce the survival time of pig kidneys and hearts in preclinical trials with different non-human primates. Furthermore, PCMV/PRV has been transmitted in the first pig to human heart xenotransplantation and contributed to the death of the patient. Although transmitted to the recipient, there is no evidence that PCMV/PRV can infect primate cells including human cells. PCMV/PRV is closely related to the human herpesviruses 6 and 7, and only distantly related to the human CMV (HCMV). Antiviral drugs used for the treatment of HCMV are less effective against PCMV/PRV. However, there are well described strategies to eliminate the virus from pig facilities. In order to detect the virus and to eliminate it, highly sensitive detection methods and the knowledge of how, where and when to screen the donor pigs is required. Here, a comparative testing of organs from pigs of different ages using polymerase chain reaction (PCR)-based and immunological methods was performed. Testing young piglets, PCMV/PRV was detected effectively by PCR in blood, bronchoalveolar lavage fluid, tonsils and heart. In adult animals, detection by PCR was not successful in most cases, because the virus load was below the detection limit or the virus was in its latent stage. Therefore, detection of antibodies against selected recombinant proteins corresponding to epitopes detected by nearly all infected animals in a Western blot assay is advantageous. By contrast, immunological testing is not beneficial in young animals as piglets might have PCMV/PRV-specific antibodies obtained from their infected mother via the colostrum. Using a thoughtful combination of PCR-based and immunological methods, detection of PCMV/PRV in donor pigs for xenotransplantation is feasible and a controlled elimination of the virus by early weaning or other methods is possible.

show abstract

Tolerating CD47

Isenberg,

Montero

2024

Clinical & Translational Med

View full text Add to dashboard Cite

Cluster of differentiation 47 (CD47) occupies the outer membrane of human cells, where it binds to soluble and cell surface receptors on the same and other cells, sculpting their topography and resulting in a pleiotropic receptor‐multiligand interaction network. It is a focus of drug development to temper and accentuate CD47‐driven immune cell liaisons, although consideration of on‐target CD47 effects remain neglected. And yet, a late clinical trial of a CD47‐blocking antibody was discontinued, existent trials were restrained, and development of CD47‐targeting agents halted by some pharmaceutical companies. At this point, if CD47 can be exploited for clinical advantage remains to be determined. Herein an airing is made of the seemingly conflicting actions of CD47 that reflect its position as a junction connecting receptors and signalling pathways that impact numerous human cell types. Prospects of CD47 boosting and blocking are considered along with potential therapeutic implications for autoimmune diseases and cancer.

show abstract

Porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV): A threat for xenotransplantation?

Cited by 19 publications

References 42 publications

Early testing of porcine organ xenotransplantation products in humans: Microbial safety as illustrated for porcine cytomegalovirus

Early testing of porcine organ xenotransplantation products in humans: Microbial safety as illustrated for porcine cytomegalovirus

How, where and when to screen for porcine cytomegalovirus (PCMV) in donor pigs for xenotransplantation

Tolerating CD47

Contact Info

Product

Resources

About