Homologies entre les deux rétrovirus BLV et HTLV-1 et développement d’une nouvelle approche thérapeutique basée sur la levée de la latence virale

Abstract

Homologies between BLV and HTLV-1 retroviruses and development of a novel therapeutic approach based on induction of viral expression. BLV (bovine leukemia virus) and HTLV-1 (human T-cell leukemia virus) are related retroviruses inducing leukemia (BLV and HTLV-1) or inflammatory diseases (HTLV-1) in the bovine and the human species respectively. The diseases are characterized by an apparent lack of viral expression in many infected cells in vivo. A humoral and a cellular immune response directed against viral antigens is continuously present. In fact, these two viruses have developed a series of mechanisms tightly controlling their expression, thereby allowing escape from the immune surveillance. Among these, chromatin compaction plays an essential role in the transcriptional regulation of the virus. The level of chromatin compaction is the result of an interplay between antagonistic actions of two families of enzymes: HATs (histone acetyltransferases) and HDACs (histone deacetylases) which, respectively, incorporate or withdraw histone acetyl groups. HDAC inhibitors induce a decondensation of chromatin and consequently increase the transcription. Thus, latent infected cells are forced to express viral proteins and are destroyed by the immune response. This viral gene activation therapy might be a novel approach for the treatment of BLV and HTLV-1 induced diseases.

Keywords

• HDAC inhibitor
• viral latency