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

doi:10.1186/1742-4690-6-83

Retrovirology

Volume 6

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Shoji T
Higuchi M
Kondo R
Takahashi M
Oie M
Tanaka Y
Aoyagi Y
Fujii M

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Higuchi M
Kondo R
Takahashi M
Oie M
Tanaka Y
Aoyagi Y
Fujii M
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Research

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

Toshiyuki Shoji¹^,2^* , Masaya Higuchi¹^* , Rie Kondo¹ , Masahiko Takahashi¹ , Masayasu Oie¹ , Yuetsu Tanaka³ , Yutaka Aoyagi² and Masahiro Fujii¹

¹Division of Virology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan

²Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata 951-8510, Japan

³Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Uehara 207, Nishihara-cho, Nakagami-gun, Okinawa 903-0215, Japan

author email corresponding author email* Contributed equally

Retrovirology 2009, 6:83doi:10.1186/1742-4690-6-83


Published:	17 September 2009

Abstract

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-kappaB2 (NF-κB2)/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-κB2 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.

Conclusion

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.