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Human T cell leukemia virus type 2 (HTLV-2) Tax2 has a dominant activity over HTLV-1 Tax1 to immortalize human CD4+ T cells

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Abstract

While human T cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T cell leukemia, a close relative, HTLV-2, is not associated with any leukemia. HTLV-1 and HTLV-2 encode the Tax1 and Tax2 proteins, respectively, which are essential for the immortalization of human T cells by the respective viruses, thereby causing persistent infection. In this study, we compared Tax1 and Tax2 with respect to their immortalization activity in human T cells. Lentivirus-mediated transduction of the tax2 gene into human peripheral blood mononuclear cells stimulated with phytohemagglutinin and interleukin-2 in 96-well plates induced outgrowing T cells in most wells, but the cells infected with the control viruses died within 3 weeks. Surprisingly, the number of outgrowing cells induced by Tax2 was much higher than that induced by Tax1, and the appearance of outgrowing cells by Tax2 was earlier than that induced by Tax1. Nevertheless, both Tax2 and Tax1 preferentially immortalized CD4+ T cells, but not CD8+ T cells. Our study showed that HTLV-2 Tax2 can immortalize human CD4+ T cells, and the activity is much higher than that of Tax1. The distinct T cell immortalization activities of Tax2 and Tax1 might therefore play a role in the different pathogeneses observed for these two viruses.

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Acknowledgments

We would like to thank Dr. Hiroyuki Miyoshi at RIKEN Tsukuba Institute for providing the lentivirus plasmids, and Dr. Renaud Mahieux and Dr. William Hall for providing the anti-Tax2 antibody and tax2B gene, respectively. We also wish to thank the Takeda Pharmaceutical Company for providing recombinant human IL-2. We would like to express our gratitude to Misako Tobimatsu for the excellent technical assistance. This study was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas and for Scientific Research (C) of Japan, as well as a Grant for the Promotion of Niigata University Research Projects.

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Authors and Affiliations

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

    Michitaka Imai, Masaya Higuchi, Manami Yoshita, Masahiko Takahashi, Masayasu Oie, Hideaki Matsuki & Masahiro Fujii

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

    Michitaka Imai & Yutaka Aoyagi

  3. Department of Immunology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Niigata, 951-8510, Japan

    Hiroki Kawamura

  4. Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan

    Yuetsu Tanaka

Authors
  1. Michitaka Imai
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  2. Masaya Higuchi
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  3. Hiroki Kawamura
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  4. Manami Yoshita
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  5. Masahiko Takahashi
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  6. Masayasu Oie
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  7. Hideaki Matsuki
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  8. Yuetsu Tanaka
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  9. Yutaka Aoyagi
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  10. Masahiro Fujii
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Corresponding author

Correspondence to Masahiro Fujii.

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The first two authors contributed equally to this study.

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Imai, M., Higuchi, M., Kawamura, H. et al. Human T cell leukemia virus type 2 (HTLV-2) Tax2 has a dominant activity over HTLV-1 Tax1 to immortalize human CD4+ T cells. Virus Genes 46, 39–46 (2013). https://doi.org/10.1007/s11262-012-0831-9

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