1. HTLV-2 Tax Immortalizes Human CD4+ Memory T Lymphocytes by Oncogenic Activation and Dysregulation of Autophagy.
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Tong Ren, Wen Dong, Takahashi, Yoshinori, Di Xiang, Yunsheng Yuan, Xin Liu, Loughran Jr., Thomas P., Shao-Cong Sun, Hong-Gang Wang, and Hua Cheng
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T cells , *LEUKEMIA , *AUTOPHAGY , *PROTEINS , *MITOGENS - 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-establishedTcell lines.Wefurther 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 humanTcells and also implicated Tax2 in serving as a molecular tool to generate distinct T cell subtype lines. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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