HTLV-2 tax immortalizes human CD4+ memory T lymphocytes by oncogenic activation and dysregulation of autophagy

Tong Ren, Wen Dong, Yoshinori Takahashi, Di Xiang, Yunsheng Yuan, Xin Liu, Thomas P. Loughran, Shao Cong Sun, Hong-Gang Wang, Hua Cheng

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Human T cell leukemia virus type 1 and type 2 (HTLV-1 and -2) are two closely related retroviruses with the former causing adult T cell leukemia. HTLV-2 infection is prevalent among intravenous drug users, and the viral genome encodes the viral transactivator Tax, which is highly homologous to the transforming protein Tax from HTLV-1. However, the link between HTLV-2 infection and leukemia has not been established. In the present study, we evaluated the activity of HTLV-2 Tax in promoting aberrant proliferation of human CD4 T lymphocytes. Tax2 efficiently immortalized CD4+ memory T lymphocytes with a CD3/TCRαβ/CD4/CD25/CD45RO/CD69 immunophenotype, promoted constitutive activation of PI3K/Akt, IκB kinase/NF-κB, mitogen-activated protein kinase, and STAT3, and it also increased the level of Mcl-1. Disruption of these oncogenic pathways led to growth retardation and apoptotic cell death of the Tax2-established T cell lines. We further found that Tax2 induced autophagy by interacting with the autophagy molecule complex containing Beclin1 and PI3K class III to form the LC3+ autophagosome. Tax2-mediated autophagy promoted survival and proliferation of the immortalized T cells. The present study demonstrated the oncogenic properties of Tax2 in human T cells and also implicated Tax2 in serving as a molecular tool to generate distinct T cell subtype lines.

Original languageEnglish (US)
Pages (from-to)34683-34693
Number of pages11
JournalJournal of Biological Chemistry
Volume287
Issue number41
DOIs
StatePublished - Oct 5 2012

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Human T-lymphotropic virus 2
T-cells
Autophagy
Lymphocyte Activation
Taxation
Chemical activation
T-Lymphocytes
Data storage equipment
Deltaretrovirus Infections
Human T-lymphotropic virus 1
Phosphatidylinositol 3-Kinases
tax Gene Products
Deltaretrovirus
Cell Line
Adult T Cell Leukemia Lymphoma
Trans-Activators
Viral Genome
Retroviridae
Drug Users
Mitogen-Activated Protein Kinases

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Ren, Tong ; Dong, Wen ; Takahashi, Yoshinori ; Xiang, Di ; Yuan, Yunsheng ; Liu, Xin ; Loughran, Thomas P. ; Sun, Shao Cong ; Wang, Hong-Gang ; Cheng, Hua. / HTLV-2 tax immortalizes human CD4+ memory T lymphocytes by oncogenic activation and dysregulation of autophagy. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 41. pp. 34683-34693.
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abstract = "Human T cell leukemia virus type 1 and type 2 (HTLV-1 and -2) are two closely related retroviruses with the former causing adult T cell leukemia. HTLV-2 infection is prevalent among intravenous drug users, and the viral genome encodes the viral transactivator Tax, which is highly homologous to the transforming protein Tax from HTLV-1. However, the link between HTLV-2 infection and leukemia has not been established. In the present study, we evaluated the activity of HTLV-2 Tax in promoting aberrant proliferation of human CD4 T lymphocytes. Tax2 efficiently immortalized CD4+ memory T lymphocytes with a CD3/TCRαβ/CD4/CD25/CD45RO/CD69 immunophenotype, promoted constitutive activation of PI3K/Akt, IκB kinase/NF-κB, mitogen-activated protein kinase, and STAT3, and it also increased the level of Mcl-1. Disruption of these oncogenic pathways led to growth retardation and apoptotic cell death of the Tax2-established T cell lines. We further found that Tax2 induced autophagy by interacting with the autophagy molecule complex containing Beclin1 and PI3K class III to form the LC3+ autophagosome. Tax2-mediated autophagy promoted survival and proliferation of the immortalized T cells. The present study demonstrated the oncogenic properties of Tax2 in human T cells and also implicated Tax2 in serving as a molecular tool to generate distinct T cell subtype lines.",
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HTLV-2 tax immortalizes human CD4+ memory T lymphocytes by oncogenic activation and dysregulation of autophagy. / Ren, Tong; Dong, Wen; Takahashi, Yoshinori; Xiang, Di; Yuan, Yunsheng; Liu, Xin; Loughran, Thomas P.; Sun, Shao Cong; Wang, Hong-Gang; Cheng, Hua.

In: Journal of Biological Chemistry, Vol. 287, No. 41, 05.10.2012, p. 34683-34693.

Research output: Contribution to journalArticle

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T1 - HTLV-2 tax immortalizes human CD4+ memory T lymphocytes by oncogenic activation and dysregulation of autophagy

AU - Ren, Tong

AU - Dong, Wen

AU - Takahashi, Yoshinori

AU - Xiang, Di

AU - Yuan, Yunsheng

AU - Liu, Xin

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AU - Sun, Shao Cong

AU - Wang, Hong-Gang

AU - Cheng, Hua

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