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 infection 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 technique using a monoclonal antibody (C11D8) directed against an epitope of the viral surface glycoprotein (SU). Positive staining of the central nervous system (CNS) capillary endothelial cells with no labeling on neuronal or glial cells was observed in cats that were inoculated with the virus mixture. This was in contrast to brain tissue of cats infected with FeLV-C alone, which showed no such staining. While non-CNS endothelial cells derived from human umbilical vein (HUVEC) could be readily infected in culture by FeLV-C, endothelial cells derived from human retina (REC) or brain (BEC) were resistant to infection by this parental virus. These latter cells in 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-derived endothelial cells. Using polymerase chain reaction and DNA sequencing strategies to amplify and analyze DNA fragments of the proviral SU region from cells infected with REC-selected viruses, we found the occurrence of a single recombinant in which two-thirds of the SU gene from the N-terminus of FeLV-C was replaced by the endogenous FeLV element. This recombinant virus, when molecularly cloned, should be useful in determining its potential in vivo neuropathogenicity.
Chakrabarti
R
R
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033.
Hofman
F M
FM
Pandey
R
R
Mathes
L E
LE
Roy-Burman
P
P
D000741:Anemia, Aplastic / Q000378:metabolism / Q000382:microbiology; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism / Q000382:microbiology*; D002415:Cats; D004279:DNA, Viral / Q000032:analysis; D004730:Endothelium, Vascular / Q000378:metabolism / Q000382:microbiology*; D007124:Immunoenzyme Techniques; D005256:Leukemia Virus, Feline / Q000235:genetics*; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D013047:Specific Pathogen-Free Organisms; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
D004279:DNA, Viral; D014759:Viral Envelope Proteins