Understanding HTLV-I Protease

AbstractHuman T cell leukemia virus type I (HTLV-I) is a human retrovirus that has been clinically associated with adult T cell leukemia/lymphoma, and it has been designated as a dangerous emerging pathogen by the Centers for Disease Control. Like other retroviruses, proteolytic processing of specific sites in polyprotein precursors by a retroviral protease is an essential step in the viral life cycle. HTLV-I protease is a 28 kDa homodimeric aspartic acid protease that has only modest homology to other retroviral proteases. The enzymology of HTLV-I protease has only recently begun to be investigated, and although it shares many characteristics of other retroviral proteases, it exhibits distinct substrate specificity and different susceptibility to aspartic acid protease inhibitors. This review describes what has been reported to date on the structural characterization, specificity, and inhibition of HTLV-I protease