Viral Aetiology of Adult T-Cell Leukaemia

Yamamoto, Naoki; Hinuma, Yorio

doi:10.1099/0022-1317-66-8-1641

Cited by 52 publications

(21 citation statements)

References 67 publications

(100 reference statements)

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“…3 is an exogenous retrovirus that infects 10ϳ20 million people worldwide (1)(2)(3)(4). Although the majority of infected individuals remain lifelong asymptomatic carriers, HTLV-1 is also etiologically associated with adult T cell leukemia (ATL) and a range of inflammatory diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis, which is a chronic disease of the CNS (1-3).…”

Section: H Uman T Cell Leukemia Virus Type 1 (Htlv-1)mentioning

confidence: 99%

“…Although the majority of infected individuals remain lifelong asymptomatic carriers, HTLV-1 is also etiologically associated with adult T cell leukemia (ATL) and a range of inflammatory diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis, which is a chronic disease of the CNS (1-3). HTLV-1-infected lymphocytes produce very few infectious cell-free virions, and the virus is mainly transmitted via cell-cell contacts (2,4,5). Therefore, HTLV-1 transmission between individuals occurs by the transfer of infected lymphocytes through breast milk, semen, or blood (4,6).…”

Section: H Uman T Cell Leukemia Virus Type 1 (Htlv-1)mentioning

confidence: 99%

“…Therefore, HTLV-1 transmission between individuals occurs by the transfer of infected lymphocytes through breast milk, semen, or blood (4,6). In vitro, HTLV-1 is capable of transforming CD4 ϩ T cells into continuously growing T cell lines (2,3). The potent viral transactivator Tax is known to activate both the HTLV-1 long terminal repeat and the promoters of various cellular genes, leading to strong promotion of cell proliferation and activation (7).…”

Section: H Uman T Cell Leukemia Virus Type 1 (Htlv-1)mentioning

confidence: 99%

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Tax-Inducible Production of CC Chemokine Ligand 22 by Human T Cell Leukemia Virus Type 1 (HTLV-1)-Infected T Cells Promotes Preferential Transmission of HTLV-1 to CCR4-Expressing CD4+ T Cells

Hieshima

Nagakubo

Nakayama

et al. 2008

The Journal of Immunology

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Adult T cell leukemia is a mature CD4+ T cell malignancy which predominantly expresses CCR4 and is etiologically associated with human T cell leukemia virus type 1 (HTLV-1). Because HTLV-1 transmission depends on close cell-cell contacts, HTLV-1-infected T cells may preferentially interact with CCR4+CD4+ T cells for efficient viral transmission. In terms of gene expression and protein secretion, we found a strong correlation between HTLV-1 Tax oncoprotein and CCL22, a CCR4 ligand, in HTLV-1-infected T cells. Transient Tax expression in an HTLV-1-negative T cell line activated the CCL22 promoter and induced CCL22. Additionally, tax gene knockdown by small interference RNA reduced CCL22 expression in the infected T cells. These findings indicate that CCL22 is a cellular target gene of Tax. In chemotaxis assays, the culture supernatants of HTLV-1-infected T cells selectively attracted CCR4+CD4+ T cells in PBMCs. This was blocked by pretreating the supernatants with anti-CCL22 Ab or PBMCs with a synthetic CCR4 antagonist. In coculture experiments, primary CCR4+CD4+ T cells significantly adhered to Tax-expressing cells. This adhesion was blocked by the CCR4 antagonist or pertussis toxin. Interestingly, CCR4 was redistributed to the contact region, and in some cases, this was accompanied by a polarized microtubule-organizing center, which is an indicator of virological synapse formation, in the infected T cells. Finally, anti-CCL22 Ab treatment also blocked HTLV-1 transmission to primary CD4+ T cells in coculture experiments with HTLV-1 producer cells. Thus, HTLV-1-infected T cells produce CCL22 through Tax and selectively interact with CCR4+CD4+ T cells, resulting in preferential transmission of HTLV-1 to CCR4+CD4+ T cells.

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Section: H Uman T Cell Leukemia Virus Type 1 (Htlv-1)mentioning

confidence: 99%

Section: H Uman T Cell Leukemia Virus Type 1 (Htlv-1)mentioning

confidence: 99%

Section: H Uman T Cell Leukemia Virus Type 1 (Htlv-1)mentioning

confidence: 99%

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Tax-Inducible Production of CC Chemokine Ligand 22 by Human T Cell Leukemia Virus Type 1 (HTLV-1)-Infected T Cells Promotes Preferential Transmission of HTLV-1 to CCR4-Expressing CD4+ T Cells

Hieshima

Nagakubo

Nakayama

et al. 2008

The Journal of Immunology

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“…1,2 In vitro, HTLV-1 efficiently immortalizes CD4 ϩ T cells into continuously growing T-cell blasts. 3 HTLV-1 is vertically transmitted from mother to child through breast feeding and also horizontally by sexual contact.…”

Section: Introductionmentioning

confidence: 99%

Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1–transformed T cells

Yoshie

Fujisawa

Nakayama

et al. 2002

Blood

273

248

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“…Adult T-cell leukemia (ATL) is a highly aggressive malignancy of mature CD4 þ CD25 þ T cells etiologically associated with human T-cell leukemia virus type 1 (HTLV-1; Yamamoto and Hinuma, 1985). HTLV-1 encodes a potent viral transactivator Tax that activates the HTLV-1 long terminal repeat (LTR) and also induces the expression of various cellular target genes, including those encoding cytokines, cytokine receptors, chemokines, cell adhesion molecules and nuclear transcriptional factors, collectively leading to the strong promotion of cell proliferation (Yoshida, 2001;Grassmann et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia

et al. 2007

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Viral Aetiology of Adult T-Cell Leukaemia

Cited by 52 publications

References 67 publications

Tax-Inducible Production of CC Chemokine Ligand 22 by Human T Cell Leukemia Virus Type 1 (HTLV-1)-Infected T Cells Promotes Preferential Transmission of HTLV-1 to CCR4-Expressing CD4+ T Cells

Tax-Inducible Production of CC Chemokine Ligand 22 by Human T Cell Leukemia Virus Type 1 (HTLV-1)-Infected T Cells Promotes Preferential Transmission of HTLV-1 to CCR4-Expressing CD4+ T Cells

Frequent expression of CCR4 in adult T-cell leukemia and human T-cell leukemia virus type 1–transformed T cells

Aberrant expression of Fra-2 promotes CCR4 expression and cell proliferation in adult T-cell leukemia

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