High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis

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Abstract
Adult T cell leukemia (ATLL) develops in 3 - 5% of HTLV-1 carriers after a long period of latency during which a persistent polyclonal expansion of HTLV-1 infected lymphocytes is observed in all individuals. This incubation period is significantly shortened in HTLV-1 carrier with Strongyloides stercoralis (Ss) infection, suggesting that Ss could be a cofactor of ATLL. As an increased T cell proliferation at the asymptomatic stage of HTLV-1 infection could increase the risk of malignant transformation, the effect of Ss infection on infected T lymphocytes was assessed in vivo in HTLV-1 asymptomatic carriers. After real-time quantitative PCR, the mean circulating HTLV-1 proviral load was more than five times higher in HTLV-1 carriers with strongyloidiasis than in HTLV-1+ individuals without Ss infection (P<0.009). This increased proviral load was found to result from the extensive proliferation of a restricted number of infected clones, i.e. from oligoclonal expansion, as evidenced by the semiquantitative amplification of HTLV-1 flanking sequences. The positive effect of Ss on clonal expansion was reversible under effective treatment of strongyloidiasis in one patient with parasitological cure whereas no significant modification of the HTLV-1 replication pattern was observed in an additional case with strongyloidiasis treatment failure. Therefore, Ss stimulates the oligoclonal proliferation of HTLV-1 infected cells in HTLV-1 asymptomatic carriers in vivo. This is thought to account for the shortened period of latency observed in ATLL patients with strongyloidiasis. Oncogene (2000) 19, 4954 - 4960