• Refine Query
  • Source
  • Publication year
  • to
  • Language
  • 2
  • 1
  • Tagged with
  • 5
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 2
  • 1
  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Rôle et devenir de PML lors de l’infection par l’EMCV / Role and fate of PML during EMCV infection

Maroui, Mohamed Ali 14 February 2012 (has links)
PML et les corps nucléaires (CN) sont impliqués dans la défense antivirale. En effet, notre équipe a montré que la surexpression de PMLIII confère la résistance au virus de la stomatite vésiculaire, au virus de l'influenza, au virus foamy mais pas au virus de l’encéphalomyocardite (EMCV). J’ai montré dans mon travail de thèse que l’EMCV contrecarre le pouvoir antiviral de PMLIII en induisant sa dégradation par un processus dépendant du protéasome et de SUMO. Cependant, les cellules de souris invalidées pour PML sont plus sensibles à l’infection par l’EMCV que les cellules issues de souris parentales. Pour déterminer l’isoforme de PML responsable de cet effet antiviral, j’ai analysé l’effet des sept isoformes de PML (PMLI-VII) et j’ai montré que seule l’expression en stable de PMLIV confère la résistance à l’EMCV en séquestrant la polymérase virale 3Dpol au sein des CN PML. De plus la déplétion de PMLIV augmente la production de l’EMCV dans les cellules traitées par l’interféron. Ces données indiquent le mécanisme par lequel PML confère la résistance à l’EMCV et révèlent que PML est l’une des protéines médiatrices des effets anti-EMCV de l’interféron. / PML and nuclear bodies (NBs) are implicated in antiviral defense. Indeed, our team showed that overexpression of PMLIII confers resistance to vesicular stomatitis virus, influenza virus, foamy virus but not to encephalomyocarditis virus (EMCV). I have shown during my thesis that EMCV counteracts the antiviral effect of PMLIII by inducing its degradation in SUMO and proteasome-dependent way. However, cells derived from PML knockout mice are more susceptible to EMCV infection than wild-type cells. To determine the isoforme of PML implicated in this antiviral effect, I analysed the effect of the seven PML isoforms (PMLI-PMLVII) and I showed that only stable expression of PMLIV confers resistance to EMCV by sequestring the viral polymérase 3Dpol in PML Nbs. In addition, depletion of PMLIV boosted EMCV production in interferon-treated cells. These finding sindicate the mechanism by which PML confers resistance to EMCV and reveal a new pathway mediating the antiviral activity of interferon against EMCV.
2

Rôle et devenir de PML lors de l'infection par l'EMCV

Maroui, Mohamed Ali 14 February 2012 (has links) (PDF)
PML et les corps nucléaires (CN) sont impliqués dans la défense antivirale. En effet, notre équipe a montré que la surexpression de PMLIII confère la résistance au virus de la stomatite vésiculaire, au virus de l'influenza, au virus foamy mais pas au virus de l'encéphalomyocardite (EMCV). J'ai montré dans mon travail de thèse que l'EMCV contrecarre le pouvoir antiviral de PMLIII en induisant sa dégradation par un processus dépendant du protéasome et de SUMO. Cependant, les cellules de souris invalidées pour PML sont plus sensibles à l'infection par l'EMCV que les cellules issues de souris parentales. Pour déterminer l'isoforme de PML responsable de cet effet antiviral, j'ai analysé l'effet des sept isoformes de PML (PMLI-VII) et j'ai montré que seule l'expression en stable de PMLIV confère la résistance à l'EMCV en séquestrant la polymérase virale 3Dpol au sein des CN PML. De plus la déplétion de PMLIV augmente la production de l'EMCV dans les cellules traitées par l'interféron. Ces données indiquent le mécanisme par lequel PML confère la résistance à l'EMCV et révèlent que PML est l'une des protéines médiatrices des effets anti-EMCV de l'interféron.
3

NMR studies of the structure, dynamics and interactions of the conserved RNA motifs of the EMCV picornavirus

Mohammed, Sadia January 2012 (has links)
The conserved secondary structural RNA motifs of EncephaloMyoCarditis Virus (EMCV) have been well characterised biochemically and shown to play an important role in translation initiation by a novel cap-independent mechanism called Internal Ribosomal Entry Site (IRES). However, the three dimensional structure and interactions of these conserved motifs are not known, and hence the mechanism is not fully understood. The NMR results described in this thesis have provided, for the first time, new structural knowledge on the conformation of these motifs, their affinity for Mg2+ and their intermolecular interactions. RNA motifs selected from two separate domains (I and J) of the IRES structure were investigated using a range of 2D and 3D NMR techniques. The apical ‘hammerhead’ region of the I domain contains a highly conserved 16mer RNA which hosts a stable and mutationally sensitive G547CGA550 tetraloop. Sequence specific assignments were carried out on this motif, along with its Mg2+ complex, and a large number of NMR experimental constraints were generated for the RNA structure determination. Similarly, high resolution NMR structures of a distal 17mer RNA, which has been predicted to be a potential receptor for the GCGA tetraloop, and its Mg2+ complex were also produced. Thus, we were able to demonstrate that Mg2+ stabilises the RNA tertiary structure via non-specific interactions. Since the largest changes were induced at the tetraloop motif, we propose that Mg2+ stabilises the 16mer into an optimum conformation which is essential for IRES function. The determination of the structures of the above motifs led us to investigate the 16mer-17mer binary (1:1) complex at 1 GHz, in the presence of Mg2+. Significant changes were observed in the 1H and 31P chemical shift, NOE intensity and line width, clearly demonstrating RNA-RNA interactions taking place between the two components. The most interesting result to emerge was the distinct absence of NOEs from G547{NH} of the stable tetraloop, thus highlighting an important structural role for this functionally critical residue. Since no previous work has shown a clear interaction between the two RNAs, the results obtained in this project provide the first direct experimental evidence for intramolecular interactions in the I domain of EMCV IRES.Finally, we show how isotopically labelled RNAs can be successfully used as an aid in NMR assignment, analysis and structure determination. The J domain of EMCV IRES binds to eIF4GII protein and is essential for translation initiation. A suite of 3D NMR techniques were carried out on a highly enriched and uniformly 13C, 15N-labelled 39mer RNA. Several key features of the RNA, which may be involved in protein recognition, were identified. Further, a selectively 19F-labelled 16mer RNA from the I domain, was also studied to show how fluorine NMR can be used to probe RNA structure, dynamics and interactions. The RNA motifs of the EMCV IRES were shown to exhibit high stabilities, which are brought about by the complex folding of the various secondary structural elements involving RNA- Mg2+, RNA-RNA and RNA-protein tertiary interactions. It is these vital interactions that enable the IRES to recruit the ribosome in the translation initiation step of protein synthesis, and have laid a strong foundation for further NMR investigation of the whole IRES.
4

INHIBITION OF HOST INNATE IMMUNE RESPONSES THROUGH THE MODULATION OF CYTOPLASMIC STRESS GRANULES BY ENCEPHALOMYOCARDITIS VIRUS PROTEASE / 脳心筋炎ウイルス(EMCV)プロテアーゼによる細胞性ストレス顆粒形成の制御と抗ウイルス自然免疫応答の阻害機構

Ng Chen Seng 24 September 2014 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(生命科学) / 甲第18627号 / 生博第318号 / 新制||生||42(附属図書館) / 31527 / 京都大学大学院生命科学研究科統合生命科学専攻 / (主査)教授 藤田 尚志, 教授 米原 伸, 教授 朝長 啓造 / 学位規則第4条第1項該当 / Doctor of Philosophy in Life Sciences / Kyoto University / DFAM
5

Investigating the Role of PIR1 and CD200R1 in the Innate Immune Response to Viral Pathogens

MacKay, Christopher R. 30 May 2017 (has links)
After initially being infected with a virus, before an adaptive immune response can be mounted, the innate immune system of a cell recognizes and responds to certain patterns present in pathogenic molecules. I studied the role of two genes—PIR1 and CD200R1—on the innate immune responses in two different mouse models of viral infection, infection with the picornavirus EMCV (encephalomyocarditis virus) and infection with HSV-1 (herpes simplex virus) in a mouse model of herpes simplex encephalitis, respectively. PIR1 is a putative RNA phosphatase that has been shown to play an important role in antiviral small RNA processing in C. elegans. It has also been shown to interact with the RIG-I-like receptor LGP2 in preliminary mammalian experiments. I sought to characterize the effect PIR1 has on the innate immune response to the virus EMCV in mice. By developing a PIR1-null mouse, I have found that the role of PIR1 in the progression of EMCV in mice is limited. However, in vitro studies show that PIR1 might play an important role in regulating foreign RNA recognition during the earliest time points post-infection. CD200R1 is an anti-inflammatory signaling molecule that is expressed on myeloidderived cells, and whose ligand is highly expressed within the central nervous system. I investigated the role of this receptor in an intracranial model of herpes simplex encephalitis. CD200R1KO mice show improved survival following direct intracranial infection with HSV. I found this increased survival can be attributed to decreased levels of viral replication in CD200R1KO compared to wild-type mice. Further investigation has shown that CD200R1 affects the signaling and upregulation of the pattern-recognition receptor TLR-2 (toll-like receptor 2), and thus CD200R1 may impact HSV-1 replication by affecting TLR2 signaling.

Page generated in 0.0223 seconds