Identification of a novel motif responsible for the distinctive transforming activity of human T-cell leukemia virus (HTLV) type 1 Tax1 protein from HTLV-2 Tax2.
BACKGROUND
Human T-cell leukemia virus type 1 (HTLV-1) is a causative agent of adult T-cell leukemia (ATL), whereas its relative HTLV-2 is not associated with any malignancies including ATL. HTLV-1 Tax1 transformed a T-cell line from interleukin (IL)-2-dependent growth to IL-2-independent growth, with an activity that was much more potent in comparison to HTLV-2 Tax2. This distinction was mediated by at least two Tax1 specific functions, an interaction with host cellular factors through the PDZ domain binding motif (PBM) and the activation of NF-kappa B2 (NF-kappa B2)/p100.


RESULTS
Using a series of Tax1 chimeric proteins with Tax2, we found that amino acids 225-232 of Tax1, the Tax1(225-232) region, was essential for the activation of NF-kappa B2 as well as for the high transforming activity. The strict amino acid conservation of Tax1(225-232) among HTLV-1 and simian T-cell leukemia virus type 1 (STLV-1), but not HTLV-2 and STLV-2, indicates that function(s) through the Tax1(225-232) region are biologically significant. Interestingly, another HTLV-1 relative, HTLV-3, has a PBM, but does not conserve the Tax1(225-232) motif in Tax3, thus indicating that these two motifs classify the three HTLVs into the separate groups.


CONCLUSIONS
These results suggest that the combinatory functions through Tax1(225-232) and PBM play crucial roles in the distinct biological properties of the three HTLVs, perhaps also including their pathogenesis.
Shoji
Toshiyuki
T
Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan. shoji-t@med.niigata-u.ac.jp
Higuchi
Masaya
M
Kondo
Rie
R
Takahashi
Masahiko
M
Oie
Masayasu
M
Tanaka
Yuetsu
Y
Aoyagi
Yutaka
Y
Fujii
Masahiro
M
D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D017124:Conserved Sequence; D016356:Gene Products, tax / Q000235:genetics / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000472:pathogenicity*; D015367:Human T-lymphotropic virus 2 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D015458:Leukemia, T-Cell / Q000821:virology; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis; D030282:Primate T-lymphotropic virus 3 / Q000235:genetics; D011994:Recombinant Proteins; D015303:Simian T-lymphotropic virus 1 / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology*
D016356:Gene Products, tax; D016328:NF-kappa B; D011994:Recombinant Proteins; C514970:tax protein, Human T-lymphotrophic virus 1; C514971:tax protein, Human T-lymphotrophic virus 2