Cellular interaction of functional porcine endogenous retrovirus

Human cells might display mechanisms counteracting infections by porcine endogenous retroviruses (PERV) in the course of pig‐to‐human xenotransplantation. Mammals have developed a number of protective strategies against viruses, including an intracellular antiretroviral defense as part of the innate immunity. In addition to the conventional innate and acquired immune responses an array of dominant genes have evolved that are constitutively expressed which suppress or prevent retroviral infections. Several of these antiretroviral restriction mechanisms have been identified including members of the tripartite motif (TRIM) and APOBEC families. The TRIM5 class of inhibitors appears to target incoming retroviral capsids and the APOBEC class of cytidine deaminases hypermutates and destabilizes retroviral genomes. Our data show that human and porcine cytidine deaminases inhibit PERV replication significantly, thereby reducing the infectious risk raised by PERV in vitro. The exact mechanism of the TRIM5 mediated restriction has not been exactly determined so far. Data published by Wood et al. (2009) indicate that PERV are insensitive to restriction by divergent TRIM5 molecules including human and monkey TRIM5α?proteins. The role of pig TRIM5 has not been clarified. We have identified a single TRIM5 gene in the pig genome. The impact of porcine TRIM5 protein on PERV will be tested using the human TRIM5α as a negative control, expecting that PERV will be insensitive to porcine TRIM5.