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Étude de la régulation de l'expression des gènes tardifs du virus d'Epstein-Barr

Abstract : The Epstein-Barr virus (EBV) is a human Herpersvirus belonging to the subfamily of γ-Herpesvirinae. EBV genes expression is tightly regulated, in a sequential manner and begins with the expression of immediate early genes whose products control the expression of early genes. Products of these allow the viral DNA synthesis and late genes expression. Mechanisms controlling immediate early and early genes expression are well documented, in contrast to those controlling late genes expression. Indeed, it is known that late genes are expressed after viral DNA replication. Furthermore, late genes promoters have a different structure of those of immediate early, early and cellular genes. They are essentially characterized by the presence of a TATT box instead of the canonical TATA-box. EBV has the feature to encode for a TBP-like, BcRF1 protein that is essential but not sufficient for late viral genes expression and that binds specifically to the TATT sequence of the late viral promoters. Our goal was primarily to identify the set of viral proteins necessary for late EBV genes expression. Thus, we have demonstrated that in addition to the BcRF1 protein, EBV encode for five other proteins necessary for late viral genes expression: BFRF2, BGLF3, BVLF1, BDLF4 and BDLF3.5. These six viral proteins form a complex enables to recruit the RNA polymerase II on the late viral promoters. We have named this complex vPIC (viral Pre-Initiation Complex) by analogy with the cellular complex of transcription initiation, formed around the TATA-Binding Protein (TBP). The vPIC is conserved in β- and γ-Herpesvirus subfamilies, but not in the α-Herpesvirus subfamily. Furthermore, our results suggest that vPIC interacts with the viral DNA replication complex, which can explain the link between viral DNA replication and late viral genes transcription. These results bring new insights to the mechanisms regulating late EBV genes expression and provide a basis for the search of new antiviral drugs.
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https://tel.archives-ouvertes.fr/tel-01699060
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  • HAL Id : tel-01699060, version 1

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Valentin Aubry. Étude de la régulation de l'expression des gènes tardifs du virus d'Epstein-Barr. Virologie. Université de Lyon, 2016. Français. ⟨NNT : 2016LYSEN029⟩. ⟨tel-01699060⟩

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