A pig virus in the xenoheart. How bad is the news?

As you probably know, the first patient with a pig heart died two months after the transplant surgery. You probably heard also that a porcine cytomegalovirus (PCMV) may have contributed to the death. However, if you are still wondering how bad is the news for the future of xentransplantation, Linda Scobie from Glasgow Caledonian University is the one to listen to. She leads a research group interested in viral zoonoses in the context of novel technologies such as xenotransplantation, and the contribution and/or reactivation of viruses in chronic disease conditions. Professor Scobie is a member of the World Health Organisation committee for the global consultation on regulatory requirements for xenotransplantation trials. I reached her by email for a feature just published in Le Scienze, the Italian edition of Scientific American. Below you can read her answers.

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Did the cytomegalovirus news take you by surprise?
LS: I would prefer not to use the word surprise as it is inappropriate in this context. This was a fully approved study by the FDA and would have had rigorous protocols in place to reduce all possible risk therefore it is necessary now for us to find out why this has occurred and share with the field.

Is it difficult to screen pigs for cytomegalovirus?
LS: This is the first instance of a heart xenotransplant in to a human and it is important for the field to learn lessons on all aspects that are of concern with this technology. It has not yet been formally proven that the PCMV detected is the cause of the patient mortality and it is more than likely a multifactorial contribution which needs to be evaluated fully.

Screening for PCMV can be complex in pigs due to its nature. This virus can exist in a latent state, meaning it is essentially ‘hiding’ in the system making it difficult to determine the virus in pigs. Indeed in herds where PCMV is endemic adult pigs can be asymptomatic making it difficult to confirm. Serology carried out in the UK, for example, indicates that over 90% of herds have been exposed to infection; this is about the same prevalence as that for human CMV. In the same way as in human allo-transplant patients, a combination of stress and other factors can lead to viral reactivation.

Normally PCR is used for detection from donor samples to detect viral DNA. Immunohistochemistry and other techniques can be supportive to indicate the presence of virus. Commercial assays are available for detecting antibody to PCMV in animals.

What would you suggest to make sure it doesn’t happen again?
LS: As indicated above, guidance provided by the FDA would have been followed and confirmed that appropriate procedures were in place regarding animal husbandry and detection. With this in mind we can assume that the donor animal was negative. If PCMV was present in the patient xenotransplant and the donor was negative, then it is important for us to revisit detection methods.

Again as there is much suggested in the literature, this would be an issue for the whole field to address in terms of agreeing a method for testing the donor animals for PCMV. This is something the community has been working on.

In my opinion the breeding approach utilising caesarean derived animals or early weaning removing neonates from the sow at the earliest possible opportunity has been documented/suggested many times and shown in the literature to be sufficient. Facilities involved in the provision of any donor organs/tissues would be following this procedure.

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