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

doi:10.1074/jbc.m112.377143

Cited by 34 publications

(53 citation statements)

References 47 publications

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“…As shown in Fig. 3H, co-localization of mKate2-LC3 and LAMP1, a lysosome marker protein, was observed as evidenced by forming yellow puncta in cells transfected with Tid1 or IKK␤ KA , a kinase active form of IKK␤ that was known to promote autophagy flux (29,30). Together, these results suggested that Tid1 and Hsp70 were both positive regulators of macroautophagy pathway, and they appeared to mediate autophagy under various stresses.…”

Section: Tid1 Induces Formation Of Lc3ϩmentioning

confidence: 51%

“…DNA transfection for HEK293 cells was performed with PolyFect reagent (Qiagen) and for HT1080 and HeLa cells with FuGENE HD (Promega, Madison, WI) following the manufacturer's recommended protocols. The methods for lentivirus production, purification, and transduction were reported previously (29).…”

Section: Methodsmentioning

confidence: 99%

“…Anti-␤-actin blot was used for the protein loading control. The heat shock procedure and GST pulldown were reported previously (29,31). For starvation, NIH3T3 or U2OS cells were washed once with PBS and then incubated with EBSS for 30 min, 1 h, and 2 h. For rapamycin stimulation, cells were incubated with rapamycin or DMSO for 6 h or overnight.…”

Section: Methodsmentioning

confidence: 99%

“…Cell Lines, Antibodies, and Reagents-HeLa, U2OS, and HT1080 cell lines were described previously (7,29), MT-1 was kindly provided by Drs. Atsushi Koito and Takeo Ohsugi, and NIH3T3 and HOS cells (human osteosarcoma cells) were obtained from the AIDS Reagent Program.…”

Section: Methodsmentioning

confidence: 99%

“…Plasmids, DNA Transfection, and Lentivirus TransductionThe expression plasmids for Tid1, Tax, Hsp70, IKK␤KA, GFP-LC3, p40PX-GFP, Beclin1, PI3KC3, and UVRAG were described previously (3,29). Tid1⌬J, Tid1L⌬N67, and Tid1L⌬N100 were generated by PCR-based site-directed mutagenesis.…”

Section: Methodsmentioning

confidence: 99%

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Tid1, the Mammalian Homologue of Drosophila Tumor Suppressor Tid56, Mediates Macroautophagy by Interacting with Beclin1-containing Autophagy Protein Complex

Niu

Zhang

Liu

et al. 2015

Journal of Biological Chemistry

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Section: Tid1 Induces Formation Of Lc3ϩmentioning

confidence: 51%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Tid1, the Mammalian Homologue of Drosophila Tumor Suppressor Tid56, Mediates Macroautophagy by Interacting with Beclin1-containing Autophagy Protein Complex

Niu

Zhang

Liu

et al. 2015

Journal of Biological Chemistry

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High levels of CC-chemokine expression and downregulated levels of CCR5 during HIV-1/HTLV-1 and HIV-1/HTLV-2 coinfections

Barrios

Castillo

et al. 2015

J. Med. Virol.

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The human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 are common copathogens among Human Immunodeficiency Virus (HIV)-infected individuals. HTLV-2 may confer a survival benefit among patients with HIV-1/HTLV-2 coinfections, along with lower plasma HIV-1 levels and delayed rates of CD4(+) T-cell decline. These effects have been attributed to the ability of the HTLV-2 viral transactivating Tax2 protein to induce the production of high levels of antiviral CC-chemokines and to downregulate expression of the CCR5 receptor, resulting in impaired entry of HIV-1 into CD4(+) T-cells. This study investigated the innate immunity of coinfected HIV/HTLV individuals by testing the ability of patient PBMCs to produce CC-chemokines in association CCR5 receptor modulation. The cellular proliferative responses of HIV/HTLV coinfected versus HIV monoinfected individuals were also evaluated. Higher levels of MIP-1α, MIP-1β, and RANTES (P < 0.05) were found in HIV-1/HTLV-2 coinfected group compared to HIV-1 monoinfected population. Upregulated levels of RANTES were shown in HIV-1/HTLV-1 after 1 and 3 days of culture (P < 0.05). Lymphocytes from HIV-1/HTLV-2 coinfected individuals showed significant CCR5 downregulation after 1 and 3 days of culture compared to lymphocytes from HIV-1 and uninfected groups (P < 0.05). Lower percentages of CCR5-positive cells were found in HIV-1/HTLV-1 coinfected after 3 days of incubation (P < 0.05). Levels of proliferation were significantly higher in the HIV-1/HTLV-1 group compared to HIV-1 alone (P < 0.05). HTLV-2 and HTLV-1 infections may induce the involvement of innate immunity against HIV-1 via stimulation of CC-chemokines and receptors, potentially modifying CCR5/HIV-1 binding and HIV-1 progression in coinfected individuals.

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Two distinct effector memory cell populations of WT1 (Wilms’ tumor gene 1)-specific cytotoxic T lymphocytes in acute myeloid leukemia patients

Nakae

Oka

Fujiki

et al. 2015

Cancer Immunol Immunother

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Wilms' tumor gene 1 (WT1) protein is a promising tumor-associated antigen for cancer immunotherapy. We have been performing WT1 peptide vaccination with good clinical responses in over 750 patients with leukemia or solid cancers. In this study, we generated single-cell gene-expression profiles of the effector memory (EM) subset of WT1-specific cytotoxic T lymphocytes (CTLs) in peripheral blood of nine acute myeloid leukemia patients treated with WT1 peptide vaccine, in order to discriminate responders (WT1 mRNA levels in peripheral blood decreased to undetectable levels, decreased but stayed at abnormal levels, were stable at undetectable levels, or remained unchanged from the initial abnormal levels more than 6 months after WT1 vaccination) from non-responders (leukemic blast cells and/or WT1 mRNA levels increased relative to the initial state within 6 months of WT1 vaccination) prior to WT1 vaccination. Cluster and principal component analyses performed using 83 genes did not discriminate between responders and non-responders prior to WT1 vaccination. However, these analyses revealed that EM subset of WT1-specific CTLs could be divided into two groups: the "activated" and "quiescent" states; in responders, EM subset of the CTLs shifted to the "quiescent" state, whereas in non-responders, those shifted to the "activated" state following WT1 vaccination. These results demonstrate for the first time the existence of two distinct EM states, each of which was characteristic of responders or non-responders, of WT1-specific CTLs in AML patients, and raises the possibility of using advanced gene-expression profile analysis to clearly discriminate between responders and non-responders prior to WT1 vaccination.

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HTLV-2 Tax Immortalizes Human CD4+ Memory T Lymphocytes by Oncogenic Activation and Dysregulation of Autophagy

Cited by 34 publications

References 47 publications

Tid1, the Mammalian Homologue of Drosophila Tumor Suppressor Tid56, Mediates Macroautophagy by Interacting with Beclin1-containing Autophagy Protein Complex

Tid1, the Mammalian Homologue of Drosophila Tumor Suppressor Tid56, Mediates Macroautophagy by Interacting with Beclin1-containing Autophagy Protein Complex

High levels of CC-chemokine expression and downregulated levels of CCR5 during HIV-1/HTLV-1 and HIV-1/HTLV-2 coinfections

Two distinct effector memory cell populations of WT1 (Wilms’ tumor gene 1)-specific cytotoxic T lymphocytes in acute myeloid leukemia patients

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