Infection by porcine endogenous retrovirus after islet xenotransplantationin SCID mice

Animal donors such as pigs could provide an alternative source of organs fo r transplantation. However, the promise of xenotransplantation is offset by the possible public health risk of a cross-species infection(1,2). All pig s contain several copies of porcine endogenous retroviruses (PERV)(3,4), an d at least three variants of PERV can infect human cell lines in vitro in c o-culture, infectivity and pseudotyping experiments(3,5-7). Thus, if xenotr ansplantation of pig tissues results in PERV viral replication, there is a risk of spreading and adaptation of this retrovirus to the human host. C-ty pe retroviruses related to PERV are associated with malignancies of haemato poietic lineage cells in their natural hosts(8). Here we show that pig panc reatic islets produce PERV and can infect human cells in culture. After tra nsplantation into NOD/SCID (non-obese diabetic, severe combined immunodefic iency) mice, we detect ongoing viral expression and several tissue compartm ents become infected. This is the first evidence that PERV is transcription ally active and infectious cross-species in vivo after transplantation of p ig tissues. These results show that a concern for PERV infection risk assoc iated with pig islet xenotransplantation in immunosuppressed human patients may be justified.