Aspects virologiques de l’infection par HTLV-1 et nouveaux concepts thérapeutiques

Abstract

HTLV-1 was the first human oncogenic retrovirus to be discovered. It is the etiological agent of adult T leukemia/lymphoma (ATLL) and of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM), two diseases that develop after a long latency period. Importantly, HTLV-1 does not cause ATLL through insertional mutagenesis. Apart from the gag, pro, pol and env genes, which are common to all retroviruses, HTLV-1 genome also encodes regulatory and auxiliary viral proteins. Among the former, Tax promotes cell transformation and HBZ is involved in the leukemic cells proliferation and in the maintenance of the transformed phenotype. Anti-ATLL therapies have lately made significant progress with an efficient antiviral treatment against the chronic and smoldering forms of this leukemia, but an efficient treatment of TSP/HAM patients is still lacking. Results from a recent study associating histone acetylase inhibitor with an anti-viral drug will be discussed here. While an increase in proviral load is considered a marker for disease progression, this treatment allows a significant drop of the proviral load in asymptomatic carriers.

Pneumopathie interstitielle diffuse révélant la leucémie-lymphome à cellules T de l’adulte HTLV1+

“…L'HTLV-1 est un rétrovirus oncogène responsable de la leucémie/lymphome à cellules T de l'adulte (ATL). La prévalence de l'ATL est de l'ordre de 2,5% chez les porteurs du virus, elle atteint les adultes après une longue période de latence, avec un pic d'incidence entre 50-69 ans, majoritairement les hommes, son pronostic reste sévère en raison de la résistance à la chimiothérapie et à l'immunosuppression profonde [ 6 – 8 ]. L'HTLV1 peut entrainer des désordres inflammatoires dans différents organes même en l'absence d'ATL [ 7 ].…”