Molecular targeting for treatment of human T-lymphotropic virus type 1 infection

• Published in: Biomedicine & pharmacotherapy Vol. 109; pp. 770 - 778
• Main Authors: Soltani, Arash, Hashemy, Seyed Isaac, Zahedi Avval, Farnaz, Soleimani, Anvar, Rafatpanah, Houshang, Rezaee, Seyed Abdorahim, Griffith, Renate, Mashkani, Baratali
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.01.2019; Elsevier
• Subjects: Adult T-cell leukemia-lymphoma (ATLL); Antiviral therapy; Human T-cell lymphotropic virus 1 (HTLV-1); Integrase; Protease; Reverse transcriptase; Human T-cell lymphotropic virus 1 (HTLV-1); Integrase; Antiviral therapy; Adult T-cell leukemia-lymphoma (ATLL); Reverse transcriptase; Protease
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2018.10.139

[Display omitted] •A limited number of HIV-1 reverse transcriptase inhibitors can limit viral replication in HTLV-1 infected cells.•AZT/IFN-α combination therapy has induced a rapid and durable response in ATLL patients.•No significant response was observed in the HTLV-1 carriers with raltegravir therapy.•Ritonavir displayed some ex vivo activity through inhibition of NF-κB activity, rather HTLV-1 protease.•Niclosamide induces degradation of the Tax protein in the proteasome. Human T-cell lymphotropic virus type 1 (HTLV-1) infection is linked to adult T-cell leukemia-lymphoma (ATLL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and several other disorders. ATLL occurs in approximately 5% of the 15–20 million people infected by HTLV-1 in the world. In general, ATLL is resistant to chemotherapy, which underlines the need for new and effective therapeutic strategies. Previous studies highlighted the role of viral enzymes, responsible for viral replication, and regulatory proteins such as Tax and HBZ in the progression of HTLV-1-associated diseases. There are conflicting reports on the efficacy of current enzyme inhibitors, mainly developed against human immunodeficiency virus (HIV), for treatment of HTLV-1 infection. New treatment approaches including monoclonal antibodies show promising results and exert significant cytotoxic effects on ATLL cells. This manuscript reviews the recent developments in molecular targeting for treatment of HTLV-1 infection.