Two-step nature of human T-cell leukemia virus type 1 replication in experimentally infected squirrel monkeys (Saimiri sciureus)

After experimental infection of squirrel monkeys (Saimiri sciureus) with hu man T-cell leukemia virus type 1 (HTLV-1)-infected cells, the virus is tran scribed only transiently in circulating blood, spleen, and lymph nodes. Sta ble disappearance of viral expression occurs at 2 to 3 weeks after inoculat ion. This coincides with the development of the anti-HTLV-l immune response and persistent detection of the provirus in peripheral blood mononuclear c ells (PBMCs). In this study, the HTLV-1 replication pattern was analyzed ov er time in PBMCs and various organs from two HTLV-1-infected squirrel monke ys. Real-time quantitative PCR confirmed that PBMCs and lymphoid organs con stitute the major reservoirs for HTLV-1. The PCR amplification of HTLV-1 Ba nking sequences from PBMCs evidenced a pattern of clonal expansion of infec ted cells identical to that observed in humans. Dissemination of the virus in body compartments appeared to result from cellular transport of the inte grated provirus. The circulating proviral burden increased as a function of time in one animal studied over a period of 4 years. The high proviral loa ds observed in the last samples resulted from the accumulation of infected cells via the extensive proliferation of a restricted number of persistent clones on a background of polyclonally expanded HTLV-l-positive cells. Ther efore, HTLV-1 primary infection in squirrel monkeys is a two-step process i nvolving a transient phase of reverse transcription followed by persistent multiplication of infected cells. This suggests that the choice of the targ et for blocking HTLV-1 replication might depend on the stage of infection.