Risk of pathogenic virus transmission by somatic cell nuclear transfer: implications for xenotransplantation

Using somatic cell nuclear transfer for the generation of cloned and transgenic animals bears the risk of transmission of viruses, either by the oocyte or by the introduced donor cell. There is evidence that the zona pellucida (ZP) surrounding the oocyte prevents virus infection; however, virus infections despite intact ZP were reported. Furthermore, the protective ZP has to be penetrated to place the somatic cell in the oocyte's perivitelline space during SCNT. Transmission of viruses also represents a severe problem during in vitro fertilization (IVF). Genetically modified and IVF-produced pigs serve as an important biomedical model for numerous diseases and it is important to evaluate whether infections of the model animals can falsify the research data. Of special significance is this topic in the case of xenotransplantation using genetically modified pigs as donor animals, because transmission of porcine viruses may be harmful to the human recipient. This was repeatedly demonstrated in preclinical pig to non-human primate trials. Therefore, donor pigs, oocytes used for SCNT, and genetically modified donor cells should be screened for potentially zoonotic viruses when creating genetically modified pigs designed for xenotransplantation.