The protease of human T-cell leukemia virus type-1 is a potential therapeutic target.
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.
Tözsér
József
J
Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, Debrecen University, Debrecen, Hungary. tozser@indi.biochem.dote.hu
Weber
Irene T
IT
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D015490:HTLV-I Infections / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use
D011480:Protease Inhibitors; D016282:Aspartic Acid Endopeptidases; C079711:HTLV-1 protease