Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein Suppression of Multilineage Hematopoiesis of CD34<sup>+</sup>Cells In Vitro

Tripp, Adam; Liu, Yingxian; Sieburg, Michelle; Montalbano, JoAnne; Wrzesinski, Stephen H.; Feuer, Gerold

doi:10.1128/jvi.77.22.12152-12164.2003

Cited by 28 publications

(57 citation statements)

References 106 publications

(61 reference statements)

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“…Collectively, the phenotypes displayed by Tax-2 in these models are consistent with Tax-2 retaining a less robust transformation potential in comparison to Tax-1. Furthermore, the ability of Tax-1 to induce G 0 /G 1 cell cycle arrest in HPCs and suppress hematopoiesis, in distinct contrast to Tax-2, allows speculation that the fate of infected HPCs following HTLV-1 and HTLV-2 infection may be fundamentally different in vivo (Tripp et al, 2003;Feuer, unpublished observations).…”

Section: Distinct Tax-1 and Tax-2 Activitiesmentioning

confidence: 99%

“…Lentivirus-mediated transduction of Tax-1 in HPCs suppressed hematopoiesis in vitro and led to increased cell cycle arrest in G 0 /G 1 . Tax-1 transduced HPCs displayed concomitant activation of endogenous p21 cip1/waf1 and p27 kip1 expression (Tripp et al, 2003) (Tripp and Feuer, unpublished observations). Interestingly, Tax-2 failed to arrest HPCs in G 0 /G 1 , failed to suppress hematopoiesis and did not detectably modulate endogenous p21 cip1/waf1 and p27 kip1 gene expression.…”

Section: Role Of Nfjb and Creb/atf In Htlv Tax-mediated Transformationmentioning

confidence: 99%

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Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2

2005

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Section: Distinct Tax-1 and Tax-2 Activitiesmentioning

confidence: 99%

Section: Role Of Nfjb and Creb/atf In Htlv Tax-mediated Transformationmentioning

confidence: 99%

Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2

2005

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“…ϩ hematopoietic progenitor cells in comparison to Tax2 (11,34,50,60,61). Tax1 and Tax2 also demonstrate unique patterns of subcellular localization in lymphoid cells (35).…”

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confidence: 99%

Proinflammatory Cytokine Gene Induction by Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Tax in Primary Human Glial Cells

Banerjee¹,

Rochford²,

Antel

et al. 2007

J Virol

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Infection with human T-cell leukemia virus type 1 (HTLV-1) can result in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic inflammatory disease of the central nervous system (CNS). HTLV-2 is highly related to HTLV-1 at the genetic level and shares a high degree of sequence homology, but infection with HTLV-2 is relatively nonpathogenic compared to HTLV-1. Although the pathogenesis of HAM/TSP remains to be fully elucidated, previous evidence suggests that elevated levels of the proinflammatory cytokines in the CNS are associated with neuropathogenesis. We demonstrate that HTLV-1 infection in astrogliomas results in a robust induction of interleukin-1␤ (IL-1␤), IL-1␣, tumor necrosis factor alpha (TNF-␣), TNF-␤, and IL-6 expression. HTLV encodes for a viral transcriptional transactivator protein named Tax that also induces the transcription of cellular genes. To investigate and compare the effects of Tax1 and Tax2 expression on the dysregulation of proinflammatory cytokines, lentivirus vectors were used to transduce primary human astrocytomas and oligodendrogliomas. The expression of Tax1 in primary human astrocytomas and oligodendrogliomas resulted in significantly higher levels of proinflammatory cytokine gene expression compared to Tax2. Notably, Tax1 expression uniquely sensitized primary human astrocytomas to apoptosis. A Tax2/Tax1 chimera encoding the C-terminal 53 amino acids of the Tax1 fused to the Tax2 gene (Tax 221 ) demonstrated a phenotype that resembled Tax1, with respect to proinflammatory cytokine gene expression and sensitization to apoptosis. The patterns of differential cytokine induction and sensitization to apoptosis displayed by Tax1 and Tax2 may reflect differences relating to the heightened neuropathogenicity associated with HTLV-1 infection and the development of HAM/TSP.Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of a slow progressive neurological disease, HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) (42). Although most HTLV-1-infected individuals remain asymptomatic carriers, an estimated 5 to 10% of HTLV-1-infected individuals develop HAM/TSP. HTLV-2 was originally isolated from a patient with an atypical hairy cell leukemia and shares ca. 70% sequence homology with HTLV-1. To date, HTLV-2 infection has been rarely and controversially linked to the development of neurodegenerative diseases (2, 30).Cytokines play a critical role in physiological processes in the central nervous system (CNS), including establishing and maintaining normal homeostasis, as well as mediating inflammatory and immune responses. Cytokines have also been implicated as being the major mediators of demyelination in the CNS, resulting in a variety of inflammatory and neoplastic diseases (1). Elevated levels of tumor necrosis factor alpha (TNF-␣), interleukin-1␤ (IL-1␤), IL-1␣, and IL-6 have previously been detected in the cerebrospinal fluid of HAM/TSP patients (28,40,57), suggesting that increased expression of these proi...

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“…It was also demonstrated that reconstitution of T lymphopoiesis with HTLV-1-infected CD34 ϩ cells in severe combined immunodeficient mice engrafted with human thymus and liver tissues (SCID-hu) resulted in the perturbation of thymopoiesis and an aberrant display of thymocyte subpopulations (13). Furthermore, it has been shown that HTLV-1 Tax-transduced hematopoietic (CD34 ϩ ) cells isolated from human fetal liver have a reduced capacity to proliferate, as evidenced by the induction of cell cycle arrest and the concomitant suppression of multilineage hematopoiesis (41,42).…”

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confidence: 99%

Human T-Cell Leukemia Virus Type 1 Tax Protein Down-Regulates Pre-T-Cell Receptor Alpha Gene Transcription in Human Immature Thymocytes

Wencker

Sausse

Derse

et al. 2007

J Virol

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The human pre-T-cell receptor alpha (TCR␣; pT␣) gene encodes a polypeptide which associates with the TCR␤ chain and CD3 molecules to form the pre-TCR complex. The surface expression of the pre-TCR is pT␣ dependent, and signaling through this complex triggers an early ␣␤ T-cell developmental checkpoint inside the thymus, known as ␤-selection. E2A transcription factors, which are involved at multiple stages of T-cell development, regulate the transcription of the pT␣ gene. Here we show that the regulatory protein Tax of the human T-cell leukemia virus type 1 (HTLV-1) efficiently suppresses the E47-mediated activation of the pT␣ promoter. Furthermore, we report that in Tax lentivirally transduced human MOLT-4 T cells, which constitutively express the pT␣ gene, the amount of pT␣ transcripts decreases. Such a decrease is not observed in MOLT-4 cells transduced by a vector encoding the Tax mutant K88A, which is unable to interact with p300. These data underline that Tax inhibits pT␣ transcription by recruiting this coactivator. Finally, we show that the expression of Tax in human immature thymocytes results in a decrease of pT␣ gene transcription but does not modify the level of E47 transcripts. These observations indicate that Tax, by silencing E proteins, down-regulates pT␣ gene transcription during early thymocyte development. They further provide evidence that Tax can interfere with an important checkpoint during T-cell differentiation in the thymus.

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Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein Suppression of Multilineage Hematopoiesis of CD34⁺Cells In Vitro

Cited by 28 publications

References 106 publications

Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2

Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2

Proinflammatory Cytokine Gene Induction by Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Tax in Primary Human Glial Cells

Human T-Cell Leukemia Virus Type 1 Tax Protein Down-Regulates Pre-T-Cell Receptor Alpha Gene Transcription in Human Immature Thymocytes

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Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein Suppression of Multilineage Hematopoiesis of CD34+Cells In Vitro

Cited by 28 publications

References 106 publications

Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2

Comparative biology of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2

Proinflammatory Cytokine Gene Induction by Human T-Cell Leukemia Virus Type 1 (HTLV-1) and HTLV-2 Tax in Primary Human Glial Cells

Human T-Cell Leukemia Virus Type 1 Tax Protein Down-Regulates Pre-T-Cell Receptor Alpha Gene Transcription in Human Immature Thymocytes

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Human T-Cell Leukemia Virus Type 1 Tax Oncoprotein Suppression of Multilineage Hematopoiesis of CD34⁺Cells In Vitro