Human T‐cell‐leukemia virus type I in post‐transfusional spastic paraparesis: Complete proviral sequence from uncultured blood cells

Abstract

Hhdman‐T‐cell‐leukemia virus type I (HTLV‐I) is the causative agent of adult T‐cell leukemia/lymphomhd (ATL) and tropical spastic paraparesis/HTLV‐I‐associated myelopathy (TSP/HAM). The different disease outcome may be attributable to subtle mutations leading to modification of viral tropism or infectivity. Initial attempts found a very high level of sequence conservation among all HTLV‐I strains. However, only one complete proviral DNA sequence is reported from a TSP/HAM patient, with a provirus derived from immortalized lymphocytes, which might be expected to be a leukemogenic variant rather than a neutrotropic one. We cloned and sequenced a complete HTLV‐I provirus (HTLV‐I_boi) derived from the uncultured lymphocytes of a sub‐acute post‐transfusional TSP/HAM patient with clonal integration of HTLV‐I. HTLV‐I_boi proviral genome is 9033 bp long, and its overall genetic organization is similar to that of the prototype HTLV‐I(ATK), without major deletions or insertions. No premature termination codon was found in the 4 open reading frames of the pX region. Divergence at the nucleotide level of HTLV‐l_Boi from the reported full‐length HTLV‐I varies from 1 to 9.4%, and indicates that it corresponds to a cosmopolitan genotype. This study did not identify specific sequences associated with neurotropic strains.