First transplantation of a pig heart from a multiple gene-modified donor, porcine cytomegalovirus/roseolovirus, and antiviral drugs.

Abstract

The porcine cytomegalovirus (PCMV) is actually a porcine roseolovirus (PRV).1 As the official International Committee on Taxonomy of Viruses (ITCV) name, suid betaherpesvirus 2 (SuBHV2),2 is not widely used, the abbreviation (PCMV/PRV) will be used to make clear that it is a herpesvirus not closely related to the human cytomegalovirus (HCMV), but to the human herpesviruses 6 and 7 (HHV-6, HHV7), which are also roseoloviruses.3 PCMV/PRV was shown to reduce significantly the survival time of pig xenotransplants in non-human primates. Yamada et al.4 and Sekijima et al.5 reported a reduction of the survival time of pig kidneys from PCMV/PRV-positive donor pigs when transplanted in cynomolgus monkeys and baboons, respectively, in 2014. Already in 2002 Mueller et al.6 reported an activation PCMV in a pig-to-primate model of xenotransplantation in animals with short survival times. In 2016 for the first time an active replication of PCMV following transplantation of a pig heart into a baboon despite undetected virus in the donor pig was reported.7 Denner et al.8 reported a reduction of the survival time of genetically modified pig hearts in baboons. For detailed reviews of these and other studies see Denner.9,10 PCMV/PRVwas also transmitted to the human recipient who received a pig heart in January 2022 in Baltimore, Maryland, USA.11 The clinical features and the steadily increasing virus load observed in the patient in Baltimore are very similar to the features and high virus load observed in baboons, which received a PCMV/PRV-positive heart in Munich.8 Therefore, it is likely that the virus contributed together with other factors to the death of the