Isolation and characterization of human T-Cell lymphotropic virus type-1 from patients with tropical spastic paraparesis

ABSTRACT

Endemic tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM) is a slowly progressive chronic neurological disorder that is manifested clinically by spastic paraperesis frequently in association with bowel and bladder dysfunction. It is one of the most common chronic neurologic disorders in many endemic foci around the world. Human T-lymphotropic virus type-1 (HTVL-I) has been etiologically associated with TSP/HAM based primarily on the high prevalence of antibodies to HTLV-I in the serum and CSF of affected patients. We report here the isolation of HTLV-I from peripheral blood lymphocytes and cerebrospinal fluid derived mononuclear cells of TSP/HAM patients by stimulation with interleukin-2 and cocultivation with umbilical cord blood mononuclear cells. Established cell lines contained HTLV-I antigen as demonstrated by immunoflourescence and cell-associated virus particles as observed by electron microscopy; low level reverse transcriptase activity was detected in cultures expressing viral antigens. Virus infected cultures were transformed in vitro as determined by their loss of contact inhibition and their continuous growth in the absence of exogenous IL-2. Of particular significance was our location of HTLV-I from three family members with TSP/HAM of varying duration and clinical severity. This study resulted in the first isolation of virus from a cluster of TSP/HAM patients within the same family, the first isolation of virus from a childhood case of TSP/HAM, and the first in vitro transformed HTLV-I infected cells from TSP/HAM patients. In addition, the methodology applied in this investigation subsequently has been used to consistently isolate virus from HTLV-I infected persons from widely separated geographic locations. This work supports a causative role for HTLV-I in the pathogenesis of TSP/HAM and helps to extend the spectrum of disease that may result from HTLV-I infection. (AU)