Tözsér József, Weber Irene T
Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, Debrecen University, Debrecen, Hungary.
Curr Pharm Des. 2007;13(12):1285-94. doi: 10.2174/138161207780618849.
Human T-cell leukemia virus type-1 (HTLV-1) is associated with a number of human diseases. Although the mechanism by which the virus causes diseases is still not known, studies indicate that viral replication is critical for the development of HTLV-1 associated myelopathy, and initial studies suggested that blocking replication with reverse transcriptase inhibitors had a therapeutic effect. Therefore, based on the success of HIV-1 protease inhibitors, the HTLV-1 protease is also a potential target for chemotherapy. Furthermore, mutated residues in HIV-1 protease that confer drug resistance are frequently seen in equivalent positions of other retroviral proteases, like HTLV-1 protease. Therefore, comparison of HTLV-1 and HIV-1 proteases is expected to aid the rational design of broad spectrum inhibitors effective against various retroviral proteases, including the mutant HIV-1 enzymes appearing in drug resistance. This review describes the characteristics of HTLV-1 protease, makes comparison with HIV-1 protease, and discusses the status of inhibitor development for the HTLV-1 protease.
人类嗜T淋巴细胞病毒1型（HTLV-1）与多种人类疾病相关。尽管该病毒引发疾病的机制尚不清楚，但研究表明病毒复制对于HTLV-1相关脊髓病的发展至关重要，并且初步研究表明用逆转录酶抑制剂阻断复制具有治疗效果。因此，基于HIV-1蛋白酶抑制剂的成功，HTLV-1蛋白酶也是化疗的潜在靶点。此外，赋予HIV-1蛋白酶耐药性的突变残基在其他逆转录病毒蛋白酶（如HTLV-1蛋白酶）的等效位置也经常出现。因此，比较HTLV-1和HIV-1蛋白酶有望有助于合理设计对各种逆转录病毒蛋白酶有效的广谱抑制剂，包括出现在耐药性中的突变HIV-1酶。本综述描述了HTLV-1蛋白酶的特性，与HIV-1蛋白酶进行了比较，并讨论了HTLV-1蛋白酶抑制剂的开发状况。
