Hepatitis C Virus (HCV) Evades NKG2D-Dependent NK Cell Responses through NS5A-Mediated Imbalance of Inflammatory Cytokines

Understanding how hepatitis C virus (HCV) induces and circumvents the host's natural killer (NK) cell-mediated immunity is of critical importance in efforts to design effective therapeutics. We report here the decreased expression of the NKG2D activating receptor as a novel strategy adopted by HCV to evade NK-cell mediated responses. We show that chronic HCV infection is associated with expression of ligands for NKG2D, the MHC class I-related Chain (MIC) molecules, on hepatocytes. However, NKG2D expression is downmodulated on circulating NK cells, and consequently NK cell-mediated cytotoxic capacity and interferon-γ production are impaired. Using an endotoxin-free recombinant NS5A protein, we show that NS5A stimulation of monocytes through Toll-like Receptor 4 (TLR4) promotes p38- and PI3 kinase-dependent IL-10 production, while inhibiting IL-12 production. In turn, IL-10 triggers secretion of TGFβ which downmodulates NKG2D expression on NK cells, leading to their impaired effector functions. Moreover, culture supernatants of HCV JFH1 replicating Huh-7.5.1 cells reproduce the effect of recombinant NS5A on NKG2D downmodulation. Exogenous IL-15 can antagonize the TGFβ effect and restore normal NKG2D expression on NK cells. We conclude that NKG2D-dependent NK cell functions are modulated during chronic HCV infection, and demonstrate that this alteration can be prevented by exogenous IL-15, which could represent a meaningful adjuvant for therapeutic intervention

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

Comment sont suivis les jeunes adultes diabétiques de type 1 non pris en charge par le secteur d endocrinologie adulte ? Quelles sont les spécificités de cette prise en charge pour le médecin traitant ? Analyse d une cohorte au CHU de Reims

REIMS-BU Santé (514542104) / SudocSudocFranceF

Comment le médecin généraliste vit-il la mort de ses patients ?

RENNES1-BU Santé (352382103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Desmodesmus sp. pigment and FAME profiles under different illuminations and nitrogen status

International audienc

Growth and production of the venerid bivalve Eurhomalea exalbida in the Beagle Channel, Tierra del Fuego

Growth, mortality and productivity of the hard clam E. exalbida from Ushuaia Bay, Beagle Channel were investigated. The parameters of the von Bertalanffy growth function were estimated to be H = 73.98 mm, K = 0.180 y 1, t0 = 0.147 y. Maximum individual production amounted to 2.742 g shell free wet mass (SFWM) at 49.5 mm shell height. Animals between 40 mm and 70 mm shell height contribute most to overall population somatic production P of 133.89 g SFWM m-2 y-1. Mean annual biomass B amounted to 1122.69 g SFWM m-2 y-1. Annual P/B ratio and mortality rate Z were estimated to 0.119 y-1 and 0.141 y-1, respectively. Slow growth and low turnover makes this population less suitable for sustainable commercial exploitation

Wood Degradation by Fomitiporia mediterranea M. Fischer: Exploring Fungal Adaptation Using Metabolomic Networking

Fomitiporia mediterranea M. Fischer (Fmed) is a white-rot wood-decaying fungus associated with one of the most important and challenging diseases in vineyards: Esca. To relieve microbial degradation, woody plants, including Vitis vinifera, use structural and chemical weapons. Lignin is the most recalcitrant of the wood cell wall structural compounds and contributes to wood durability. Extractives are constitutive or de novo synthesized specialized metabolites that are not covalently bound to wood cell walls and are often associated with antimicrobial properties. Fmed is able to mineralize lignin and detoxify toxic wood extractives, thanks to enzymes such as laccases and peroxidases. Grapevine wood’s chemical composition could be involved in Fmed’s adaptation to its substrate. This study aimed at deciphering if Fmed uses specific mechanisms to degrade grapevine wood structure and extractives. Three different wood species, grapevine, beech, and oak. were exposed to fungal degradation by two Fmed strains. The well-studied white-rot fungus Trametes versicolor (Tver) was used as a comparison model. A simultaneous degradation pattern was shown for Fmed in the three degraded wood species. Wood mass loss after 7 months for the two fungal species was the highest with low-density oak wood. For the latter wood species, radical differences in initial wood density were observed. No differences between grapevine or beech wood degradation rates were observed after degradation by Fmed or by Tver. Contrary to the Tver secretome, one manganese peroxidase isoform (MnP2l, jgi protein ID 145801) was the most abundant in the Fmed secretome on grapevine wood only. Non-targeted metabolomic analysis was conducted on wood and mycelium samples, using metabolomic networking and public databases (GNPS, MS-DIAL) for metabolite annotations. Chemical differences between non-degraded and degraded woods, and between mycelia grown on different wood species, are discussed. This study highlights Fmed physiological, proteomic and metabolomic traits during wood degradation and thus contributes to a better understanding of its wood degradation mechanisms

A 21L/BA.2-21K/BA.1 “MixOmicron” SARS-CoV-2 hybrid undetected by qPCR that screen for variant in routine diagnosis

Among the multiple SARS-CoV-2 variants identified since summer 2020, several have co-circulated, creating opportunities for coinfections and potentially genetic recombinations that are common in coronaviruses. Viral recombinants are indeed beginning to be reported more frequently. Here, we describe a new SARS-CoV-2 recombinant genome that is mostly that of a Omicron 21L/BA.2 variant but with a 3′ tip originating from a Omicron 21K/BA.1 variant. Two such genomes were obtained in our institute from adults sampled in February 2022 in university hospitals of Marseille, southern France, by next-generation sequencing carried out with the Illumina or Nanopore technologies. The recombination site was located between nucleotides 26,858-27,382. In the two genomic assemblies, mean sequencing depth at mutation-harboring positions was 271 and 1362 reads and mean prevalence of the majoritary nucleotide was 99.3 ± 2.2% and 98.8 ± 1.6%, respectively. Phylogeny generated trees with slightly different topologies according to whether genomes analyzed were depleted or not of the 3′ tip. This 3′ terminal end brought in the Omicron 21L/BA.2 genome a short transposable element of 41 nucleotides named S2m that is present in most SARS-CoV-2 except a few variants among which the Omicron 21L/BA.2 variant and may be involved in virulence. Importantly, this recombinant is not detected by currently used qPCR that screen for variants in routine diagnosis. The present observation emphasizes the need to survey closely the genetic pathways of SARS-CoV-2 variability by whole genome sequencing, and it could contribute to gain a better understanding of factors that lead to observed differences between epidemic potentials of the different variants

Heterogeneity in susceptibility to hydroxychloroquine of SARS-CoV-2 isolates

International audienc