Porcine endogenous retroviruses: in vitro host range and attempts to establish small animal models

Using transgenic pigs as the source of cells or organs for xenotransplantat ion is associated with the risk of porcine endogenous retrovirus (PERV) tra nsmission. Multiple proviruses are integrated into the genome of all pigs, and virus particles, some of which are able to infect human cells, are rele ased from normal pig cells. In order to evaluate the potential risk posed b y the transmission of PERVs, in vitro infection studies were performed as a basis for small animal as well as non-human primate models. In vitro infec tivity was demonstrated for permanent cell lines and primary cells from a w ide range of species. Productive infection was shown using reverse transcri ptase (RT) assays and RT-PCR for mink, feline and human kidney cell lines, primary rhesus peripheral blood mononuclear cells (PBMCs), and baboon splee n cells and PBMCs as well as for different human lymphoid and monocyte cell lines and PBMCs, In an attempt to establish a small animal model, naive gu inea pigs, non-immunosuppressed rats, rats immunosuppressed by cyclosporin- A and immunosuppressed rats treated with cobra venom factor were inoculated with PERVs produced from porcine kidney PK-15 cells, infected human 293 ki dney cells and mitogen-stimulated porcine PBMCs. Animals were also inoculat ed with PERV-producing PK-15 and 293 cells. No antibodies against PERV and no provirus integration were observed in any of the treated animals. This s uggests that productive infection of these animals did not occur in this ex perimental setting.