Multiple viral strategies of HTLV-1 for dysregulation of cell growth control.
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.
Yoshida
M
M
Banyu Tsukuba Research Institute, Tsukuba, Ibaraki 300-2611, Japan. yoshimx@banyu.co.jp
D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology / Q000821:virology; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000502:physiology; D002455:Cell Division; D002472:Cell Transformation, Viral / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D005260:Female; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000502:physiology*; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology* / Q000235:genetics / Q000473:pathology / Q000821:virology; D008297:Male; D008954:Models, Biological; D016328:NF-kappa B / Q000502:physiology; D014411:Neoplastic Stem Cells / Q000473:pathology / Q000821:virology; D009687:Nuclear Proteins / Q000502:physiology; D026362:Serum Response Factor; D015534:Trans-Activators / Q000502:physiology; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014779:Virus Replication
D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D016356:Gene Products, tax; D020672:I-kappa B Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D026362:Serum Response Factor; D015534:Trans-Activators; D016159:Tumor Suppressor Protein p53