Porcine cytomegalovirus in pigs being bred for xenograft organs: progress towards control

Abstract

In human medicine, human cytomegalovirus (HCMV) is readily transmitted by organ transplant causing end-organ disease and triggering graft rejection in recipients. Because of a chronic shortage of human organs, pigs transgenic for human complement control proteins are being considered as potential donors. Such xenotransplantation raises concerns about the potential zoonotic transmission of viruses including porcine cytomegalovirus (PCMV), an endemic infection of pigs. Similar to HCMV and PCMV transmission is thought to occur in utero and perinatally. We used quantitative polymerase chain reaction to examine the prevalence, organ distribution and viral load of PCMV in human decay accelerating factor (CD55) transgenic pigs. In animals reared under conventional farm conditions, virus was identified in a wide range of organs including potential xenografts (liver, kidney and heart). The spleen was PCMV DNA positive in all infected pigs. Examination of foetal spleens failed to identify evidence of transplacental infection and prospective monitoring of two litters showed that infection occurred in the postnatal period. This transmission was prevented by hysterotomy derivation and barrier rearing. Our findings demonstrate that PCMV could be eradicated from pig herds being bred for xenotransplantation and argue that the spleen from donor animals should be examined as part of quality control procedures if clinical trials proceed.

Correction of hemophilia as a proof of concept for treatment of monogenic diseases by fetal spleen transplantation

“…However, it is important to note that previous pig-to-human xenotransplantations have failed to reveal even a single instance of PERV transmission to a human subject (43). Moreover, a recent study has suggested that PERV could be eradicated from pig herds bred for xenotransplantation (44). Thus, as suggested recently by Ogata and Platt (45), although the potential danger of PERV to public health cannot be entirely dismissed, it should be approached with careful attention to the xenograft recipients, rather than necessitating that xenotransplantation studies be abandoned.…”

Determinants of High Titer in Recombinant Porcine Endogenous Retroviruses

“…However, the theoretical risk of a zoonotic, cross-species transmission of an infectious pathogen remains a concern (27,36). Whereas exogenous pathogens can be removed by specific-pathogen-free breeding, these techniques cannot exclude inherited agents such as endogenous retroviruses that are passed down via the germ line (6,34,35).…”

Absence of Replication-Competent Human-Tropic Porcine Endogenous Retroviruses in the Germ Line DNA of Inbred Miniature Swine

“…Xenotransplantation carries the concerns of cross-species transmission of infectious pathogens present in the donor species (7,17,18,23). Studies indicate that many exogenous microorganisms can be eliminated from the donor herd by using various barrier methods and specialized qualified-pathogenfree rearing techniques (3,25,26). However, porcine endogenous retroviruses (PERVs) are an exception to this rule, as proviral copies are inherited through the germ line DNA.…”