You can manage bookmarks using lists, please log in to your user account for this.
Media type:
E-Book;
Thesis
Title:
The Human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax: Impact of Tax-induced signaling on Tax protein expression and virus transmission
University thesis:
Dissertation, Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2020
Footnote:
Description:
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent for HTLV-1 associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), and adult T-cell leukemia/lymphoma (ATL), a fatal lymphoproliferative disease. In spite of infecting around 5 to 10 million people worldwide, until today, there is neither a therapeutic cure nor a protective vaccine, therefore comprehensively understanding viral mechanisms that contribute to HTLV-1 transmission and cellular transformation is of pivotal importance. It is well described that Tax, the multifaceted oncoprotein of HTLV-1, induces nuclear factor of kappa B (NF-kB) activity, an ubiquitous cellular signaling cascade that mainly regulates immune functions as a response to exogenous stimuli. Chronic deregulation of NF-kB by Tax represents a hallmark of cellular transformation and tumor development, thus, the interplay between Tax and NF-kB has been intensively characterized. This work identifies a novel positive feedback loop, which shows that NF-kB signaling regulates Tax protein expression vice versa. Expression defects of various NF-kB deficient Tax mutants could be rescued by restoring NF-kB activity. In contrast, repression of NF-kB in transfected and transformed T-cell lines led to diminished Tax protein levels. Moreover, data shown here suggest a stabilizing effect of NF-kB activity on Tax protein rather than Tax transcripts, which is dependent on the machinery of the cellular ubiquitination pathway. Next to cellular transformation, Tax plays an important role in fostering HTLV-1 cell-to-cell transmission. Tax is known to induce a variety of cellular factors in order to facilitate virus transfer. A fundamental route of transmission in vitro depict viral biofilms (VB), carbohydrate rich extracellular structures including embedded HTLV-1 viral clusters and collagens of unknown composition. This work identifies collagen type IV (COL4) as a novel and important component of the VB. Moreover, expression of collagen4alpha1 (COL4A1) and collagen4alpha1 (COL4A2) is a ...