Tyrosine 110 in the measles virus phosphoprotein is required to block STAT1 phosphorylation

AbstractThe measles virus (MV) P gene encodes three proteins: P, an essential polymerase cofactor, and C and V, which have multiple functions including immune evasion. We show here that the MV P protein also contributes to immune evasion, and that tyrosine 110 is required to block nuclear translocation of the signal transducer and activator of transcription factors (STAT) after interferon type I treatment. In particular, MV P inhibits STAT1 phosphorylation. This is shown not only by transient expression but also by reverse genetic analyses based on a new functional infectious cDNA derived from a MV vaccine vial (Moraten strain). Our study also identifies a conserved sequence around P protein tyrosine 110 as a candidate interaction site with a cellular protein

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Le théâtre communiste durant la Guerre froide

Devaux Patricia. Le théâtre communiste durant la Guerre froide. In: Revue d’histoire moderne et contemporaine, tome 44 N°1, Janvier-mars 1997. pp. 86-108

Measles Virus Phosphoprotein Gene Products: Conformational Flexibility of the P/V Protein Amino-Terminal Domain and C Protein Infectivity Factor Function

The measles virus (MV) P gene codes for three proteins: P, an essential polymerase cofactor, and V and C, which have multiple functions but are not strictly required for viral propagation in cultured cells. V shares the amino-terminal domain with P but has a zinc-binding carboxyl-terminal domain, whereas C is translated from an overlapping reading frame. During replication, the P protein binds incoming monomeric nucleocapsid (N) proteins with its amino-terminal domain and positions them for assembly into the nascent ribonucleocapsid. The P protein amino-terminal domain is natively unfolded; to probe its conformational flexibility, we fused it to the green fluorescent protein (GFP), thereby also silencing C protein expression. A recombinant virus (MV-GFP/P) expressing hybrid GFP/P and GFP/V proteins in place of standard P and V proteins and not expressing the C protein was rescued and produced normal ratios of mono-, bi-, and tricistronic RNAs, but its replication was slower than that of the parental virus. Thus, the P protein retained nearly intact polymerase cofactor function, even with a large domain added to its amino terminus. Having noted that titers of cell-associated and especially released MV-GFP/P were reduced and knowing that the C protein of the related Sendai virus has particle assembly and infectivity factor functions, we produced an MV-GFP/P derivative expressing C. Intracellular titers of this virus were almost completely restored, and those of released virus were partially restored. Thus, the MV C protein is an infectivity factor

Elaboration de nanocomposites à matrice polypropylène chargée d'argile native

Cette étude porte sur l élaboration de nanocomposites à matrice polypropylène (PP) chargée de montmorillonite native (NaMMT). La stratégie retenue est basée sur l utilisation d une phase polaire intermédiaire sous forme de mélanges maîtres, dont l élaboration est réalisée par extrusion avec injection d eau.Dans une première partie la dispersion de NaMMT et à titre de comparaison de montmorillonite modifiée par extrusion assistée eau dans le polyamide 6 (PA6) a été étudiée grâce à une analyse de la morphologie et de son influence sur les propriétés thermomécaniques. Par la suite, des mélanges maîtres à base de PA6 ont été élaborés par ce procédé et dispersés dans le PP via une compatibilisation réactive. L analyse de la morphologie, en relation avec les conditions d élaboration et les performances des mélanges nanocomposites est ensuite présentée.Dans une deuxième partie, un copolymère bloc polyether-bloc-amide (PEBA) a été utilisé comme matrice hôte de NaMMT. Sa dispersion dans le PEBA par extrusion assistée eau a été étudiée par une étude morphologique liée aux propriétés thermomécaniques et aux mécanismes de déformation. Le PEBA a ensuite été utilisé comme phase intermédiaire pour disperser NaMMT dans le PP. L analyse de la morphologie des mélanges nanocomposites est présentée, en lien avec leurs conditions d extrusion et leurs propriétés macroscopique.Finalement, la comparaison des résultats obtenus dans le cas des mélanges nanocomposites à base PA6 et PEBA est proposée afin de mettre en évidence le rôle de la polarité de la phase intermédiaire, de la rhéologie des constituants et des conditions de procédé sur les propriétés macroscopiques des matériaux.This work focuses on polypropylene (PP)/clay nanocomposites based on pristine montmorillonite (NaMMT). The elaboration strategy involves the use of a polar polymer based masterbatch to disperse NaMMT in the PP matrix. Water assisted extrusion is used to finely disperse the native montmorillonite in the polar host polymer.In the first part, the dispersion of modified and pristine montmorillonite in polyamide 6 (PA6) using water assisted extrusion is presented. The morphological analysis of the PA6 nanocomposites and its outcome on the thermomechanical properties were studied. PA6 masterbatches were then elaborated using water assisted extrusion and dispersed in PP to obtain nanocomposites blends. Their morphologies are detailed, in relation with the processing conditions, and the related mechanical properties.In the second part, polyether-block-amide (PEBA) was used as host polymer to disperse modified and native montmorillonite. Their dispersion is obtained thanks to the water assisted extrusion process. The morphological analysis and its influence onto the thermomechanical properties and on the deformation mechanisms were studied. PEBA masterbatch were then prepared using water assisted extrusion and dispersed into PP to obtain nanocomposites blends. The study of their morphologies is presented, related to the extrusion conditions, and the corresponding macroscopic performances.Finally, the comparison of the results obtained in the case of PA6 and PEBA nanocomposites blends is discussed to evidence the influence of components rheology and polarity as well as the processing conditions onto the macroscopic behaviors of the materials.LILLE1-Bib. Electronique (590099901) / SudocSudocFranceF

CD46-mediated measles virus entry: a first key to host-range specificity

International audienc

Control of C3b and C5b deposition by CD46 (membrane cofactor protein) after alternative but not classical complement activation

International audienc

Efficiency of Measles Virus Entry and Dissemination through Different Receptors

The efficiency with which different measles virus (MV) strains enter cells through the immune cell-specific protein SLAM (CD150) or other receptors, including the ubiquitous protein CD46, may influence their pathogenicity. We compared the cell entry efficiency of recombinant MV differing only in their attachment protein hemagglutinin (H). We constructed these viruses with an additional gene expressing an autofluorescent reporter protein to allow direct detection of every infected cell. A virus with a wild-type H protein entered cells through SLAM two to three times more efficiently than a virus with the H protein of the attenuated strain Edmonston, whereas cell entry efficiency through CD46 was lower. However, these subtle differences were amplified at the cell fusion stage because the wild-type H protein failed to fuse CD46-expressing cells. We also proved formally that a mutation in H protein residue 481 (asparagine to tyrosine) results in improved CD46-specific entry. To define the selective pressure exerted on that codon, we monitored its evolution in different H protein backgrounds and found that several passages in CD46-expressing Vero cells were necessary to shift it in the majority of the MV RNA. To verify the importance of these observations for human infections, we examined MV entry into peripheral blood mononuclear cells and observed that viruses with asparagine 481 H proteins infect these cells more efficiently