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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]

Background: This paper describes the study protocol of a hybrid type I randomized controlled trial that evaluates the effectiveness and cost-effectiveness of implementing Empowering African-American Women on the Road to Health (E-WORTH), an Afrocentric, group-based, computerized human immunodeficiency virus (HIV)/sexually transmitted infection (STI) prevention intervention for controlled substance-using black women in community corrections settings in New York City.Methods/design: We provide an overview of E-WORTH's hybrid type I design, which is guided by the Consolidated Framework for Implementation Research (CFIR). E-WORTH combines HIV/STI and intimate partner violence (IPV) prevention components and tests the comparative effectiveness of E-WORTH and streamlined HIV testing versus streamlined HIV testing alone in decreasing biologically confirmed HIV and STI incidence, sexual risk, and IPV, as well as in improving access to HIV and STI prevention services and care.Discussion: This paper provides an overview of E-WORTH's intervention protocol and serves as a framework for using hybrid type I designs, guided by the CFIR conceptual framework, to evaluate HIV/STI and IPV prevention interventions in community corrections settings. We discuss how E-WORTH's hybrid type I design advances implementation science through its effectiveness and cost-effectiveness aims as well as through a mixed-methods study that evaluates multilevel theory-driven factors (structural, organizational, staffing, and client) guided by the CFIR that influences the implementation of E-WORTH in a criminal justice setting. This study also addresses the novel challenges and opportunities of implementing an intervention that targets specific racial subgroup(s) in a community corrections setting that services all populations, implementing a group-based intervention with technological components in such settings, and employing community-based participatory research strategies to guide recruitment and retention efforts.Trial Registration: ClinicalTrials.gov, NCT02391233 . Registered on 17 March 2015. [ABSTRACT FROM AUTHOR]