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

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 signi®cantly 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 e ect 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 ®ve times higher in HTLV-1 carriers with stongyloidiasis than in HTLV-1+ individuals without Ss infection (P50.009). 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 ampli®-cation of HTLV-1¯anking sequences. The positive e ect of Ss on clonal expansion was reversible under e ective treatment of strongyloidiasis in one patient with parasitological cure whereas no signi®cant modi®cation 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.

Current views in HTLV-I-associated adult T-cell leukemia/lymphoma

“…Several cycles of transient active proliferation combined with chromosomal instability may be required for a clonal selection and the development of adult T-cell leukemia. In support of such a model, a high frequency of T-cell clonal expansion has been associated with chronic antigenic stimulation in carriers of S. stercoralis [122,123], and a higher frequency of leukemia has been reported in individuals carrying this parasite [124][125][126].…”

Effect of treatment of Strongyloides infection on HTLV‐1 expression in a patient with adult T‐cell leukemia

“…Alternatively, a Strongyloides antigen has been postulated to induce a potent polyclonal T-cell mitogenic response, and reactivation of HTLV-1 expression [1,20]. Although the patient's ALC and viral DNA load did not decline after ivermectin treatment, the dramatic drop in viral RNA after treatment suggests that Strongyloides was a potent stimulus for virus expression, presumably through T-cell activation.…”

“…Strongyloides stercoralis has been proposed as a cofactor for human T-cell leukemia Type 1 (HTLV-1)-associated adult T-cell leukemia-lymphoma (ATLL) [1]. This is based on epidemiologic association of Strongyloides and HTLV-1 infections in Brazil, the Caribbean Islands, and Southern Japan, and from small clinical series reporting more severe disease manifestations in the presence of both infections than with either one alone [2][3][4].…”

Reducing the global burden of HTLV-1 infection: An agenda for research and action

“…Although the genetic background, host determinants and parasitic infections (e.g. Strongyloides stercoralis) are associated with a higher probability of developing ATL and HAM-TSP, there is no biomarker able to predict future disease onset at the individual level (Gabet et al, 2000).…”