ESTABLISHMENT OF HTLV-I-INFECTED CELL-LINES FROM FRENCH, GUIANESE ANDWEST-INDIAN PATIENTS AND ISOLATION OF A PROVIRAL CLONE PRODUCING VIRAL PARTICLES

Human T-cell leukemia virus (HTLV-I) induces adult T cell leukemia/lym phoma ATL() and a chronic neurological disease named either tropical s pastic paraparesis (TSP) or HTLV-I associated myelopathy (HAM). We rep ort here the establishment and characterization of eight HTLV-I-infect ed lymphoid cell lines derived either from patients with TSP (5) or fr om asymptomatic carriers (1). Southern blot analysis of T cell beta ch ain gene rearrangements indicates that all cell lines are composed of clonal populations. The same type of analysis performed with HTLV-I-sp ecific probes showed that they harbor 1 to 5 copies of full length pro viruses often associated with deleted proviruses with a restriction ma p for BamHI, HindIII, PstI and SacI restriction enzymes resembling tho se of HTLV-I previously isolated from Japan and Carribean area. One of the cell lines, 2060, derived from a TSP patient was shown to express a relative large amount of virus easily transmissible to fresh periph eral and cord blood lymphocytes. The full length proviral genome conta ined in this cell line was cloned and used in transient expression exp eriments. We showed that the cloned provirus was able to direct the sy nthesis of the major structural viral proteins, the protease and the t ax and rex regulatory proteins. The structural viral proteins could be assembled into free particles detected in the culture medium of trans fected cells. Although the infectivity of these viral particles remain s to be determined, this new clone can be employed to examine the cell types in which this TSP-derived provirus directs viral protein synthe sis and eventually replicates. It should also prove of value in studie s on the early cellular events induced by viral products.