The Experts below are selected from a list of 9246 Experts worldwide ranked by ideXlab platform
Hélène Malet - One of the best experts on this subject based on the ideXlab platform.
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High resolution cryo-EM structure of the helical RNA-bound Hantaan virus nucleocapsid reveals its assembly mechanisms
eLife, 2019Co-Authors: Benoît Arragain, Juan Reguera, Ambroise Desfosses, Irina Gutsche, Guy Schoehn, Hélène MaletAbstract:Negative-strand RNA viruses condense their genome into helical nucleocapsids that constitute essential templates for viral Replication and transcription. The intrinsic flexibility of nucleocapsids usually prevents their full-length structural characterization at high resolution. Here we describe purification of full-length recombinant metastable helical nucleocapsid of Hantaan virus ($Hantaviridae$ family, $Bunyavirales$ order) and determine its structure at 3.3 Å resolution by cryo-electron microscopy. The structure reveals the mechanisms of helical multimerization via sub-domain exchanges between protomers and highlights nucleotide positions in a continuous positively charged groove compatible with viral genome binding. It uncovers key sites for future structure-based design of antivirals that are currently lacking to counteract life-threatening hantavirus infections. The structure also suggests a model of nucleoprotein-polymerase interaction that would Enable Replication and transcription solely upon local disruption of the nucleocapsid.
Benoît Arragain - One of the best experts on this subject based on the ideXlab platform.
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High resolution cryo-EM structure of the helical RNA-bound Hantaan virus nucleocapsid reveals its assembly mechanisms
eLife, 2019Co-Authors: Benoît Arragain, Juan Reguera, Ambroise Desfosses, Irina Gutsche, Guy Schoehn, Hélène MaletAbstract:Negative-strand RNA viruses condense their genome into helical nucleocapsids that constitute essential templates for viral Replication and transcription. The intrinsic flexibility of nucleocapsids usually prevents their full-length structural characterization at high resolution. Here we describe purification of full-length recombinant metastable helical nucleocapsid of Hantaan virus ($Hantaviridae$ family, $Bunyavirales$ order) and determine its structure at 3.3 Å resolution by cryo-electron microscopy. The structure reveals the mechanisms of helical multimerization via sub-domain exchanges between protomers and highlights nucleotide positions in a continuous positively charged groove compatible with viral genome binding. It uncovers key sites for future structure-based design of antivirals that are currently lacking to counteract life-threatening hantavirus infections. The structure also suggests a model of nucleoprotein-polymerase interaction that would Enable Replication and transcription solely upon local disruption of the nucleocapsid.
John Mclauchlan - One of the best experts on this subject based on the ideXlab platform.
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the hepatitis c virus ns4b protein can trans complement viral rna Replication and modulates production of infectious virus
Journal of Virology, 2009Co-Authors: Daniel M Jones, Paul Targettadams, Arvind H. Patel, John MclauchlanAbstract:Studies of the hepatitis C virus (HCV) life cycle have been aided by development of in vitro systems that Enable Replication of viral RNA and production of infectious virus. However, the functions of the individual proteins, especially those engaged in RNA Replication, remain poorly understood. It is considered that NS4B, one of the replicase components, creates sites for genome synthesis, which appear as punctate foci at the endoplasmic reticulum (ER) membrane. In this study, a panel of mutations in NS4B was generated to gain deeper insight into its functions. Our analysis identified five mutants that were incapable of supporting RNA Replication, three of which had defects in production of foci at the ER membrane. These mutants also influenced posttranslational modification and intracellular mobility of another replicase protein, NS5A, suggesting that such characteristics are linked to focus formation by NS4B. From previous studies, NS4B could not be trans-complemented in Replication assays. Using the mutants that blocked RNA synthesis, defective NS4B expressed from two mutants could be rescued in trans-complementation Replication assays by wild-type protein produced by a functional HCV replicon. Moreover, active Replication could be reconstituted by combining replicons that were defective in NS4B and NS5A. The ability to restore Replication from inactive replicons has implications for our understanding of the mechanisms that direct viral RNA synthesis. Finally, one of the NS4B mutations increased the yield of infectious virus by five- to sixfold. Hence, NS4B not only functions in RNA Replication but also contributes to the processes engaged in virus assembly and release.
Juan Reguera - One of the best experts on this subject based on the ideXlab platform.
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High resolution cryo-EM structure of the helical RNA-bound Hantaan virus nucleocapsid reveals its assembly mechanisms
eLife, 2019Co-Authors: Benoît Arragain, Juan Reguera, Ambroise Desfosses, Irina Gutsche, Guy Schoehn, Hélène MaletAbstract:Negative-strand RNA viruses condense their genome into helical nucleocapsids that constitute essential templates for viral Replication and transcription. The intrinsic flexibility of nucleocapsids usually prevents their full-length structural characterization at high resolution. Here we describe purification of full-length recombinant metastable helical nucleocapsid of Hantaan virus ($Hantaviridae$ family, $Bunyavirales$ order) and determine its structure at 3.3 Å resolution by cryo-electron microscopy. The structure reveals the mechanisms of helical multimerization via sub-domain exchanges between protomers and highlights nucleotide positions in a continuous positively charged groove compatible with viral genome binding. It uncovers key sites for future structure-based design of antivirals that are currently lacking to counteract life-threatening hantavirus infections. The structure also suggests a model of nucleoprotein-polymerase interaction that would Enable Replication and transcription solely upon local disruption of the nucleocapsid.
Ambroise Desfosses - One of the best experts on this subject based on the ideXlab platform.
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High resolution cryo-EM structure of the helical RNA-bound Hantaan virus nucleocapsid reveals its assembly mechanisms
eLife, 2019Co-Authors: Benoît Arragain, Juan Reguera, Ambroise Desfosses, Irina Gutsche, Guy Schoehn, Hélène MaletAbstract:Negative-strand RNA viruses condense their genome into helical nucleocapsids that constitute essential templates for viral Replication and transcription. The intrinsic flexibility of nucleocapsids usually prevents their full-length structural characterization at high resolution. Here we describe purification of full-length recombinant metastable helical nucleocapsid of Hantaan virus ($Hantaviridae$ family, $Bunyavirales$ order) and determine its structure at 3.3 Å resolution by cryo-electron microscopy. The structure reveals the mechanisms of helical multimerization via sub-domain exchanges between protomers and highlights nucleotide positions in a continuous positively charged groove compatible with viral genome binding. It uncovers key sites for future structure-based design of antivirals that are currently lacking to counteract life-threatening hantavirus infections. The structure also suggests a model of nucleoprotein-polymerase interaction that would Enable Replication and transcription solely upon local disruption of the nucleocapsid.