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Background: HTLV-I infected CD4+ T-cells lines usually progress towards a CD3- or CD3low phenotype. In this paper, we studied expression, kinetics, chromatin remodeling of the CD3 gene at different time-points post HTLV-I infection. Results: The onset of this phenomenon coincided with a decrease of CD3γ followed by the subsequent progressive reduction in CD3δ, then CD3ε and CD3ζ mRNA. Transient transfection experiments showed that the CD3γ promoter was still active in CD3- HTLV-I infected cells demonstrating that adequate amounts of the required transcription factors were available. We next looked at whether epigenetic mechanisms could be responsible for this progressive decrease in CD3 expression using DNase I hypersensitivity (DHS) experiments examining the CD3γ and CD3δ promoters and the CD3δ enhancer. In uninfected and cells immediately post-infection all three DHS sites were open, then the CD3γ promoter became non accessible, and this was followed by a sequential closure of all the DHS sites corresponding to all three transcriptional control regions. Furthermore, a continuous decrease of in vivo bound transcription initiation factors to the CD3γ promoter was observed after silencing of the viral genome. Coincidently, cells with a lower expression of CD3 grew more rapidly. Conclusion: We conclude that HTLV-I infection initiates a process leading to a complete loss of CD3 membrane expression by an epigenetic mechanism which continues along time, despite an early silencing of the viral genome. Whether CD3 progressive loss is an epiphenomenon or a causal event in the process of eventual malignant transformation remains to be investigated. [ABSTRACT FROM AUTHOR]

An abstract of the research paper titled,"The Human T-cell leukemia virus type 1 (HTLV-1) Tax protein inhibits nonsensemediated mRNA decay by interacting with INT6/EIF3E and UPF1 ," is presented.