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Title/Abstract/Keywords

ACTIVATING TRANSCRIPTION FACTOR 4 (ATF4) IS UPREGULATED BY HUMAN HERPESVIRUS 8 INFECTION, INCREASES VIRUS REPLICATION AND PROMOTES VIRUS PROANGIOGENIC PROPERTIES

Grigolato, Jessica (2013) ACTIVATING TRANSCRIPTION FACTOR 4 (ATF4) IS UPREGULATED BY HUMAN HERPESVIRUS 8 INFECTION, INCREASES VIRUS REPLICATION AND PROMOTES VIRUS PROANGIOGENIC PROPERTIES. PhD Thesis , Università degli Studi di Ferrara.

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    Abstract

    Previous results from our group demonstrate that human herpesvirus 8 (HHV-8) triggers proangiogenic behavior in endothelial cells by promoting transcriptional activation and secretion of monocyte chemoattractant protein 1 (MCP-1), through activation of Nuclear Factor κB (NF-κB). However, inhibition of NF-κB still results in partial MCP-1 induction and consequent capillary-like structure formation, suggesting the involvement of another transcriptional pathway. Here we describe that HHV-8 infection upregulates cellular activating transcription factor 4 (ATF4), a member of the CREB family involved in the cell response to ER stress. Upregulation of ATF4 promotes HHV-8 infection, whereas its silencing decreases virus replication, transcription and antigen expression. Furthermore, ATF4 silencing decreases virus-induced MCP-1 production, as well as viral induction of tube-like structures in endothelial cells. We also show that ATF4 per se activates the MCP-1 promoter and induces proangiogenic properties in transfected endothelial cells. The elucidation of molecular mechanism involved in this process will result in a better understanding of the angiogenic process, its involvement in cancer and will help in designing novel therapies to reduce growth and vascularisation of Kaposi’s sarcoma.

    Item Type:Thesis (PhD Thesis)
    Date:25 March 2013
    Tutor:Di Luca, Dario - Caselli, Elisabetta
    Coordinator:Bernardi, Francesco
    Institution:Università degli Studi di Ferrara
    PhD:XXIII Anno 2008 > BIOCHIMICA, BIOLOGIA MOLECOLARE E BIOTECNOLOGIE
    Divisions:Dipartimento > Scienze della vita e biotecnologie
    Subjects:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
    Uncontrolled Keywords:ATF4, HHV-8,angiogenesi
    Identification Number:10.5072//834
    Deposited on:23 Jun 2015 10:49

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