HOST RANGE AND INTERFERENCE STUDIES OF THREE CLASSES OF PIG ENDOGENOUS RETROVIRUS

Abstract

SP-03 Recent interest in the use of porcine organs, tissues and cells for xenotransplantation to humans has highlighted the need to characterise the properties of pig endogenous retroviruses (PERVs)1-4. Analysis of a variety of pig cells allowed us to isolate and identify three classes of infectious type C endogenous retrovirus (PERV-A, -B and -C) which have distinct env genes, but share highly homologous sequences in the rest of the genome. To study the properties of these env genes, expression plasmids for the three env genes were constructed and used to generate retrovirus vectors bearing corresponding Env proteins. Host range analyses by the vector transduction assay showed that PERV-A and PERV-B Envs have wider host ranges including several human cell lines compared with PERV-C Env which infected only 2 pig cell lines and 1 human cell line. Receptors for PERV-A and PERV-B were present on cells of some other species, including mink, rat, mouse and dog, suggesting that such species may provide useful model systems to study infection and pathogenicity of PERV. In contrast, no vector transduction was observed on non-human primate cell lines, casting doubt on the utility of non-human primates as models for PERV zoonosis. Interference studies showed that the three PERV strains use distinct receptors to each other and to a number of other type C mammalian retroviruses.