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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 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 stongyloidiasis 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.

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Acknowledgements

This work was supported by a grant from the Association pour la Recherche sur le Cancer and from the Comité départemental de la Drome de la Ligue Nationale Contre le Cancer. ASG was supported by a bursary from the centre Léon Bérard, I Leclerq and F Montreux were supported by a bursary from the Ministère de l'Enseignement Supérieur et de la Recherche. We would like to thank Pr Wattre and collaborators who kindly welcomed us in their laboratories for DNA extraction, digestion, ligation and PCR. We would also like to thank Marie-Dominique Reynaud for assistance.

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Gabet, AS., Mortreux, F., Talarmin, A. et al. High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis. Oncogene 19, 4954–4960 (2000). https://doi.org/10.1038/sj.onc.1203870

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