Localization, quantification and interaction with host factors of endogenous HTLV-1 HBZ protein in infected cells and ATL

Retrovirology

Roberto S Accolla²  Antoine Gessain¹  Giovanna Tosi²  Greta Forlani²  Carlo Bidoia²  Goutham U Raval² 

[1] Département de Virologie, Institut Pasteur, Paris, 75015, France;Department of Surgical and Morphological Sciences, School of Medicine, University of Insubria, Via Ottorino Rossi n.9, Varese, 21100, Italy

关键词: Monoclonal antibodies;    Adult T cell leukemia;    HBZ;    HTLV-1;   

Others  :  1221133
DOI  :  10.1186/s12977-015-0186-0

 received in 2015-03-31, accepted in 2015-06-24,  发布年份 2015

【 摘 要 】

Background

Human T cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of a severe form of neoplasia designated Adult T cell Leukaemia (ATL). It is widely accepted that the viral transactivator Tax-1 is the major viral product involved in the onset, but not in the maintenance, of neoplastic phenotype, as only 30–40% of ATL cells express Tax-1. It has been recently demonstrated that HBZ (HTLV-1 bZIP factor), a protein encoded by the minus strand of HTLV-1 genome, constantly expressed in infected cells and in ATL tumor cells, is also involved in the pathogenesis of leukaemia. The full role played by HBZ in oncogenesis is not clarified in detail also because of the limited availability of tools to assess quantitative expression, subcellular location and interaction of HBZ with host factors in ATL.

Results

By the use of the first reported monoclonal antibody against HBZ, 4D4-F3, generated in our laboratory it has been possible to carefully assess for the first time the above parameters in HTLV-1 chronically infected cells and, most importantly, in fresh leukemic cells from patients. Endogenous HBZ is expressed in speckle-like structures localized in the nucleus. The calculated number of endogenous HBZ molecules varies between 17.461 and 39.615 molecules per cell, 20- to 50-fold less than the amount expressed in HBZ transfected cells used by most investigators to assess the expression, function and subcellular localization of the viral protein. HBZ interacts in vivo with p300 and JunD and co-localizes only partially, and depending on the amount of expressed HBZ, not only with p300 and JunD but also with CBP and CREB2.

Conclusions

The possibility to study endogenous HBZ in detail may significantly contribute to a better delineation of the role of HBZ during HTLV-1 infection and cellular transformation.

【 授权许可】

   
2015 Raval et al.

【 图 表 】

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