Article

Virus Genes

, Volume 46, Issue 1, pp 39-46

First online:

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

  • Michitaka ImaiAffiliated withDivision of Virology, Niigata University Graduate School of Medical and Dental SciencesDivision of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
  • , Masaya HiguchiAffiliated withDivision of Virology, Niigata University Graduate School of Medical and Dental Sciences
  • , Hiroki KawamuraAffiliated withDepartment of Immunology, Niigata University Graduate School of Medical and Dental Sciences
  • , Manami YoshitaAffiliated withDivision of Virology, Niigata University Graduate School of Medical and Dental Sciences
  • , Masahiko TakahashiAffiliated withDivision of Virology, Niigata University Graduate School of Medical and Dental Sciences
  • , Masayasu OieAffiliated withDivision of Virology, Niigata University Graduate School of Medical and Dental Sciences
  • , Hideaki MatsukiAffiliated withDivision of Virology, Niigata University Graduate School of Medical and Dental Sciences
  • , Yuetsu TanakaAffiliated withDepartment of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus
  • , Yutaka AoyagiAffiliated withDivision of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences
    • , Masahiro FujiiAffiliated withDivision of Virology, Niigata University Graduate School of Medical and Dental Sciences Email author 

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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.

Keywords

HTLV-1 HTLV-2 Tax2 CD4 ATL