SOURCE AND ROUTE OF EXPOSURE INFLUENCE INFECTIVITY OF A MOLECULAR CLONE OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I

Infection with human T cell leukemia virus type I (HTLV-I) is typicall y asymptomatic, but does result in diverse diseases ranging from adult T cell leukemia to spastic neuromyelopathy. To date, differences in H TLVI provirus structure have not been correlated with pathogenic or as ymptomatic outcome of infection, Molecular clones of HTLV-I are now av ailable and represent a powerful tool to link virus structure to patho genesis, Present studies to explore in vivo infectivity and pathogenic ity of an HTLV-I molecular clone, K30p, have utilized the rabbit as a model system. This clone was administered to neonatal or adult rabbits by several different routes and infectivity and pathogenicity were ex amined, Detection of antiviral humoral immune responses, presence of p rovirus in tissue samples, and isolation of virus in cultures of blood lymphocytes were used to establish systemic HTLV-I infection. Intramu scular, but not nervous system, exposure to K30p HTLVI naked DNA resul ted in infection, Conversely, neural exposure to T cells that had been transfected with the K30p HTLV-I DNA consistently resulted in systemi c infection. Despite detection of HTLV-I provirus in brain and spinal cord of some infected rabbits, no clinical or neuropathological change s occurred. Source and route of virus exposure played a role in infect ivity, but did not influence the pathogenic outcome of HTLV-I infectio n.