RECOMBINATION BETWEEN FELINE EXOGENOUS AND ENDOGENOUS RETROVIRAL SEQUENCES GENERATES TROPISM FOR CEREBRAL ENDOTHELIAL-CELLS

Brain tissues of domestic cats that died of aplastic anemia from infec tion with either parental feline leukemia virus (FeLV), subgroup C, or a mixture of FeLV-C and recombinants between FeLV-C and an endogenous FeLV provirus were examined by the immunoperoxidase staining techniqu e using a monoclonal antibody (C11D8) directed against an epitope of t he viral surface glycoprotein (SU). Positive staining of the central n ervous system (CNS) capillary endothelial cells with no labeling on ne uronal or glial cells was observed in cats that were inoculated with t he virus mixture. This was in contrast to brain tissue of cats infecte d with FeLV-C alone, which showed no such staining. While non-CNS endo thelial cells derived from human umbilical vein (HUVEC) could be readi ly infected in culture by FeLV-C, endothelial cells derived from human retina (REC) or brain (BEC) were resistant to infection by this paren tal virus. These latter cells ill culture, however, could be infected by the viral mixture. The data suggested that at least one or more of the presumptive recombinant viruses could specifically infect CNS-deri ved endothelial cells. Using polymerase chain reaction and DNA sequenc ing strategies to amplify and analyze DNA fragments of the proviral SU region from cells infected with REC-selected viruses, we found the oc currence of a single recombinant in which two-thirds of the SU gene fr om the N-terminus of FeLV-C was replaced by the endogenous FeLV elemen t. This recombinant virus, when molecularly cloned, should be useful i n determining its potential in vivo neuropathogenicity.