PERSISTENT CLONAL PROLIFERATION OF HUMAN T-LYMPHOTROPIC VIRUS TYPE I-INFECTED CELLS IN-VIVO

Clonal proliferation of human T-lymphotropic virus type I (HTLV-I)infe cted cells has been detected by Southern blot analysis and inverse PCR in patients with adult T-cell leukemia, patients with HTLV-I-associat ed diseases, and even in asymptomatic carriers, Combining inverse PCR with Long PCR, we amplified the genomic DNA regions flanking the integ ration sites of the HTLV-I provirus to detect clones of infected cells , Inverse long PCR revealed that increased virus load was associated w ith an increase of both the number of cells in each clone and the numb er of clones. Clonal proliferations were found in both CD4- and CD8-po sitive cells in a carrier and a patient with HTLV-I-associated neuropa thy/tropical spastic paraparesis. These HTLV-1-infected clones persist ed over several years in the same carriers, and, moreover, most of the persistent clones were CD4 positive in a HTLV-I carrier, These findin gs indicate that HTLV-I infection plays an important role in the clona l expansion of lymphocytes and the prolonged survival of CD4-positive cells in vivo. Surviving T-lymphocytes may be susceptible to genetic c hanges, leading to the onset of leukemia.