Clonal integration and expression of human T-cell lymphotropic virus type I in carriers detected by polymerase chain reaction and inverse PCR.

Adult T-cell leukemia (ATL) is a neoplasm of mature helper (CD4) T lymphocytes, and human T-cell lymphotropic virus type-I (HTLV-I) has been suggested to be the causative virus of ATL. HTLV-I integrates its proviruses into random sites in host chromosomal DNA. Clonal integration has been observed in patients with ATL, including smoldering, chronic, and acute states. However, random and/or polyclonal integration has only been reported in a few asymptomatic HTLV-I carriers. To clarify the clonality of HTLV-I-infected cells in carriers, we used an inverse polymerase chain reaction (IPCR), which is more sensitive than Southern blot analysis. We used the peripheral blood momonuclear cells (PBMC) from 16 asymptomatic carriers and the separated CD4-positive cells. No cases showed either a monoclonal or polyclonal integration of the HTLV-I provirus by Southern blot. But, using IPCR, 7 of 16 cases showed either mono- or oligoclonal integration. In addition, the populations of clonal provirus in the total PBMC were frequently different from those in the CD4-positive cells. Three cases showed expression of HTLV-I tax/rex mRNA in the total PBMC, but no such expression was found in CD4-positive cells. In this study, an unexpected frequency of clonal HTLV-I provirus DNA was observed in HTLV-I carriers. These findings indicate that the clonal but nonmalignant proliferation of HTLV-I-infected cells already occurs even in HTLV-I carriers, and therefore that some other step is necessary to induce malignant proliferation.