Abstract
Myocyte enhancer factor-2 plays critical roles in HTLV-1 infection and transformation of CD4+ T cells associated with adult T cell leukemia (ATL) by stabilizing complex between Tax and CREB (HUM8P.335)
The Journal of immunology (1950), v 192(1_Supplement), pp 185-185.10
01 May 2014
Abstract
Abstract The exact molecular mechanisms regarding HTLV-1 Tax-mediated viral gene expression and CD4+ T cell transformation have yet to be fully delineated. Herein, utilizing virus infected primary CD4+ T cells and the virus-producing cell line, MT-2, we describe the role of myocyte enhancer factor-2 (MEF-2) in Tax-mediated transactivation of the LTR. Inhibition of MEF-2 expression by shRNA and its activity by HDAC9 led to reduced viral replication and HTLV-mediated T cell transformation in correlation with a heightened expression of MEF-2 in ATL patients. Mechanistically, MEF-2 was shown to be recruited to the HTLV-1 LTR followed by an assessment of MEF-2 binding site(s). A novel promoter-binding assay confirmed that MEF-2 constitutes the transcriptional complex that assembles on the LTR. Furthermore, an increase in MEF-2 expression was observed upon infection in an extent similar to CREB (the known Tax-interacting transcription factor) and HATs - p300, CBP, and p/CAF. Confocal imaging confirmed MEF-2 co-localization with Tax and these proteins were also shown to interact by co-immunoprecipitation. A number of MEF-2-integrated signaling pathways were activated during HTLV-1 infection of primary CD4+ T cells, including PI3K/Akt, NF-κB, MAPK, JAK/STAT and TGF-β possibly regulating MEF-2 activity. Overall, these studies are the first to describe the involvement and regulation of a novel transcription factor during the course of a retroviral infection and associated disease syndrome.
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Details
- Title
- Myocyte enhancer factor-2 plays critical roles in HTLV-1 infection and transformation of CD4+ T cells associated with adult T cell leukemia (ATL) by stabilizing complex between Tax and CREB (HUM8P.335)
- Creators
- Pooja Jain
- Publication Details
- The Journal of immunology (1950), v 192(1_Supplement), pp 185-185.10
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Other Identifier
- 991020545231704721