HOST-RANGE AND INTERFERENCE STUDIES OF 3 CLASSES OF PIG ENDOGENOUS RETROVIRUS

Recent interest in the use of porcine organs, tissues, and cells for x enotransplantation to humans has highlighted the need to characterize the properties of pig endogenous retroviruses (PERVs). Analysis of a v ariety of pig cells allowed us to isolate and identify three classes o f infectious type C endogenous retrovirus (PERV-A, PERV-B, and PERV-C) which have distinct env genes but have highly homologous sequences in the rest of the genome. To study the properties of these env genes, e xpression plasmids for the three env genes were constructed and used t o generate retrovirus vectors bearing corresponding Env proteins. Host range analyses by the vector transduction assay showed that PERV-A an d PERV-B Envs have wider host ranges, including several human cell lin es, compared with PERV-C Env, which infected only two pig cell lines a nd one human cell line. All PERVs could infect pig cells, indicating t hat the PERVs have a potential to replicate in pig transplants in immu nosuppressed patients. Receptors for PERV-A and PERV-B were present on cells of some other species, including mink, rat, mouse, and dog, sug gesting that such species may provide useful model systems to study in fection and pathogenicity of PERV. In contrast, no vector transduction was observed on nonhuman primate cell lines, casting doubt on the uti lity of nonhuman primates as models for PERV zoonosis. Interference st udies showed that the three PERV strains use receptors distinct from e ach other and from a number of other type C mammalian retroviruses.