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Etudes structurales et fonctionnelles des protéines virales impliquées dans le trafic intracellulaire du génome du virus de la grippe

Abstract : Influenza A virus genome, a member of the Orthomyxoviridae family, is segmented in eight negative single-stranded RNA molecules. These are entirely covered by nucleoproteins (NP) and are associated to the polymerase complex, forming the vRNPs (viral ribonucleoproteins). The virus enters the host cell by endocytosis and releases its genome in the cytoplasm. The vRNPs use the importins alpha/beta heterocomplex to reach the nucleus where the viral transcription and replication occur. The major component of the vRNPs NP may be involved in this step. As NP is an excellent candidate for antiviral drugs, we began structural studies of NP in complex with the human importin alpha 5. We obtained a first low resolution model of this complex by using the transmission electron microscopy.
In the nucleus, the vRNPs are tightly bound to the chromatin. It has been shown that M1 also binds to the chromatin. Our sedimentation studies show that vRNPs bind the hisones tails whereas M1 recognizes the globular domain of the histone octamer.
Late in the viral cycle, the newly synthetized vRNPs exit the nucleus. Our enzymatic essays and experiments of pull-down and sedimentation show
that two viral proteins NEP and M1 mediate this nuclear export of the vRNPs by interacting with the vRNPs and the cellular exportin CRM1/RanGTP. We also obtained the crystal structure of NEP C-terminal domain involved in the recognition of M1.
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https://tel.archives-ouvertes.fr/tel-00011131
Contributor : Hatice Akarsu <>
Submitted on : Tuesday, November 29, 2005 - 6:39:19 PM
Last modification on : Friday, November 6, 2020 - 3:49:45 AM
Long-term archiving on: : Friday, April 2, 2010 - 11:16:17 PM

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  • HAL Id : tel-00011131, version 1

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Citation

Hatice Akarsu. Etudes structurales et fonctionnelles des protéines virales impliquées dans le trafic intracellulaire du génome du virus de la grippe. Biochimie [q-bio.BM]. Université Joseph-Fourier - Grenoble I, 2005. Français. ⟨tel-00011131⟩

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