Viral oncoprotein Tax and regulation of the HTLV promoter

Abstract

Tax, an oncoprotein virally expressed from Human T-cell Leukemia Virus (HTLV), is a transcriptional regulator with incompletely understood functions in host cells. HTLV is a retrovirus of clade deltraretroviradae with two known sub-types (HTLV Type-1 and HTLV Type-2). HTLV-1 is associated with a subset of patients in development of an extremely aggressive blood cancer called Adult T-cell Leukemia/Lymphoma (ATLL) but HTLV-2 is not. It is known that Tax recruits host activator and co-activator proteins to binds to the integrated viral promoter region of HTLV and rapidly activate viral gene expression. Tax coding regions vary in HTLV-1 and type-2 in the predicted transcriptional activation domain. Exploring interaction surfaces of Tax with various host proteins involved may help us understand the basic transcriptional activation mechanisms that are manipulated by the HTLV-1. To investigate this, we accumulated a library of Tax expression plasmids with the Tax wild-type and mutant coding sequences from HTLV-1. The mutants collected have been established to impair transcriptions or cytoplasmic activities of Tax and include in contrast the Tax coding sequence from HTLV-2. Once the mutants were obtained, we established a stock that can be used in the future for downstream expression, purification, and activity binding assays.