Abstract
The human T cell leukemia virus-1 (HTLV-1) is a retrovirus that causes adult T cell leukemia (ATL) and neurological disorder, the tropical spastic paraparesis (HAM/TSP). The pathogenesis apparently results from the pleiotropic function of Tax protein, which is a key regulator of viral replication. Tax exerts (a) trans-activation and -repression of transcription of different sets of cellular genes through binding to groups of transcription factors and coactivators, (b) dysregulation of cell cycle through binding to inhibitors of CDK4/6, and (c) inhibition of some tumor suppressor proteins. These effects on a wide variety of cellular targets seem to cooperate in promoting cell proliferation. This is an effective viral strategy to amplify its proviral genome through replication of infected cells; ultimately it results in cell transformation and leukemogenesis.
MeSH terms
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Apoptosis
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CD4-Positive T-Lymphocytes / pathology
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CD4-Positive T-Lymphocytes / virology
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Cell Cycle
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Cell Cycle Proteins / physiology
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Cell Division
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Cell Transformation, Viral / physiology*
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Cyclic AMP Response Element-Binding Protein / physiology
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DNA-Binding Proteins / physiology
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Female
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Gene Expression Regulation, Viral
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Gene Products, tax / physiology*
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Genes, pX*
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Human T-lymphotropic virus 1 / genetics
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Human T-lymphotropic virus 1 / physiology*
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Humans
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I-kappa B Proteins / antagonists & inhibitors
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Leukemia-Lymphoma, Adult T-Cell / etiology*
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Leukemia-Lymphoma, Adult T-Cell / genetics
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Leukemia-Lymphoma, Adult T-Cell / pathology
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Leukemia-Lymphoma, Adult T-Cell / virology
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Male
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Models, Biological
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NF-kappa B / physiology
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Neoplastic Stem Cells / pathology
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Neoplastic Stem Cells / virology
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Nuclear Proteins / physiology
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Serum Response Factor
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Trans-Activators / physiology
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Transcriptional Activation
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Tumor Suppressor Protein p53 / physiology
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Virus Replication
Substances
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Cell Cycle Proteins
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Cyclic AMP Response Element-Binding Protein
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DNA-Binding Proteins
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Gene Products, tax
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I-kappa B Proteins
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NF-kappa B
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Nuclear Proteins
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Serum Response Factor
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Trans-Activators
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Tumor Suppressor Protein p53