Differential requirements for activation of integrated and transiently transfected human T-cell leukemia virus type 1 long terminal repeat.
Adult T-cell leukemia (ATL) cells contain integrated human T-cell leukemia virus type 1 (HTLV-1) proviruses. Although the exact sequence of events leading to the development of ATL remains incompletely resolved, expression of the integrated HTLV-1 long terminal repeat (LTR) is likely required at some point during the process of T-cell transformation. While much has been learned about the regulated expression of transiently transfected LTR reporter plasmids, an analysis of factors required for expression of chromosomally integrated HTLV-1 LTR has not been done. Here, we have constructed CHOK1 and HeLa cells that contain an integrated HTLV-1 LTR-luciferase gene. Using these cells, we have compared the requirements for activation of transiently transfected versus stably integrated HTLV-1 LTR. We observed different requirements for CREB, p300, and P/CAF in the expression of transiently transfected versus stably integrated HTLV-1 LTR. Furthermore, with dominant-negative mutants of CREB, p300, and P/CAF, we found that activation of integrated HTLV-1 LTR by an ambient stress signal, UV-C, proceeds through a path mechanistically distinct from that used by viral oncoprotein, Tax. Our findings point to additional complexities in the regulated expression of HTLV-1 proviruses compared with those hitherto revealed through transfection studies.
Okada
Masahiko
M
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892-0460, USA.
Jeang
Kuan-Teh
KT
D000123:Acetyltransferases / Q000502:physiology; D000818:Animals; D016466:CHO Cells; D018797:Cell Cycle Proteins / Q000502:physiology; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D016356:Gene Products, tax / Q000502:physiology; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology; D020079:Terminal Repeat Sequences; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors; D014162:Transfection; D014775:Virus Activation; D016662:Virus Integration; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D051548:Histone Acetyltransferases; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor