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The following results are related to COVID-19. Are you interested to view more results? Visit OpenAIRE - Explore.
321 Research products, page 1 of 33

  • COVID-19
  • European Commission
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  • Open Access English
    Authors: 
    Giuliano Bobba; Nicolas Hubé;
    Publisher: Springer International Publishing
    Countries: France, Italy, France
    Project: EC | DEMOS (822590)

    This chapter addresses the general research questions of the book, namely the possibility that populists in Europe can profit from a peculiar crisis such as COVID-19, and it wonders whether populists reacted in a similar way across countries or whether the institutional role they play at the national level has affected their reactions. Findings show that while populists have tried to take advantage of the crisis situation, the impossibility of taking ownership of the COVID-19 issue has made the crisis hard to be exploited. In particular, populists in power have tried to depoliticize the pandemic, whereas radical right-populists in opposition tried to politicize the crisis without gaining relevant public support though.

  • Open Access English
    Authors: 
    Damien Levard; Izaskun Buendia; Anastasia Lanquetin; Martina Glavan; Denis Vivien; Marina Rubio;
    Publisher: Elsevier BV
    Country: France
    Project: EC | ENTRAIN (813294)

    For the last two decades, researchers have placed hopes in a new era in which a combination of reperfusion and neuroprotection would revolutionize the treatment of stroke. Nevertheless, despite the thousands of papers available in the literature showing positive results in preclinical stroke models, randomized clinical trials have failed to show efficacy. It seems clear now that the existing data obtained in preclinical research have depicted an incomplete picture of stroke pathophysiology. In order to ameliorate bench-to-bed translation, in this review we first describe the main actors on stroke inflammatory and immune responses based on the available preclinical data, highlighting the fact that the link between leukocyte infiltration, lesion volume and neurological outcome remains unclear. We then describe what is known on neuroinflammation and immune responses in stroke patients, and summarize the results of the clinical trials on immunomodulatory drugs. In order to understand the gap between clinical trials and preclinical results on stroke, we discuss in detail the experimental results that served as the basis for the summarized clinical trials on immunomodulatory drugs, focusing on (i) experimental stroke models, (ii) the timing and selection of outcome measuring, (iii) alternative entry routes for leukocytes into the ischemic region, and (iv) factors affecting stroke outcome such as gender differences, ageing, comorbidities like hypertension and diabetes, obesity, tobacco, alcohol consumption and previous infections like Covid-19. We can do better for stroke treatment, especially when targeting inflammation following stroke. We need to re-think the design of stroke experimental setups, notably by (i) using clinically relevant models of stroke, (ii) including both radiological and neurological outcomes, (iii) performing long-term follow-up studies, (iv) conducting large-scale preclinical stroke trials, and (v) including stroke comorbidities in preclinical research. Highlights • The different experimental approaches may model different aspects of stroke. • Drugs need to be tested in several clinically relevant experimental stroke models. • Clot composition, type of arterial occlusion and recanalization need to be considered. • Outcomes should include acute but also long-term measurements. • Both infarct volume and behavioral deficits need to be systematically measured. • Including coexisting risk factors in preclinical stroke research is mandatory. • Performing multicenter studies may increase the reliability of preclinical results.

  • Open Access English
    Authors: 
    Laura Di Domenico; Giulia Pullano; Chiara E. Sabbatini; Pierre-Yves Boëlle; Vittoria Colizza;
    Publisher: HAL CCSD
    Country: France
    Project: ANR | DataRedux (ANR-19-CE46-0008), ANR | SPHINx (ANR-17-CE36-0008), EC | MOOD (874850)

    As countries in Europe implement strategies to control the COVID-19 pandemic, different options are chosen regarding schools. Through a stochastic age-structured transmission model calibrated to the observed epidemic in Île-de-France in the first wave, we explored scenarios of partial, progressive, or full school reopening. Given the uncertainty on children’s role, we found that reopening schools after lockdown may increase COVID-19 cases, yet protocols exist to keep the epidemic controlled. Under a scenario with stable epidemic activity if schools were closed, reopening pre-schools and primary schools would lead to up to 76% [67, 84]% occupation of ICU beds if no other school level reopened, or if middle and high schools reopened later. Immediately reopening all school levels may overwhelm the ICU system. Priority should be given to pre- and primary schools allowing younger children to resume learning and development, whereas full attendance in middle and high schools is not recommended for stable or increasing epidemic activity. Large-scale test and trace is required to keep the epidemic under control. Ex-post assessment shows that progressive reopening of schools, limited attendance, and strong adoption of preventive measures contributed to a decreasing epidemic after lifting the first lockdown. The role of children in the spread of COVID-19 is not fully understood, and the circumstances under which schools should be opened are therefore debated. Here, the authors demonstrate protocols by which schools in France can be safely opened without overwhelming the healthcare system.

  • Open Access English
    Authors: 
    Camille Aubry; Sinéad C. Corr; Sebastian Wienerroither; Céline Goulard; Ruth Jones; Amanda M. Jamieson; Thomas Decker; Luke A. J. O'Neill; Olivier Dussurget; Pascale Cossart;
    Publisher: HAL CCSD
    Countries: France, Austria
    Project: EC | MODELIST (233348), FWF | Type I interferons in inn... (P 20522)

    International audience; Synthesis of interferon-beta (IFN-beta) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-beta synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-beta production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, Delta pgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-beta gene, requiring TLR2 and bacterial internalization. Induction of IFN-beta was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-beta gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-beta gene expression.

  • Open Access
    Authors: 
    Jérémy Dufloo; Ludivine Grzelak; Isabelle Staropoli; Yoann Madec; Laura Tondeur; François Anna; Stéphane Pelleau; Aurélie Wiedemann; Cyril Planchais; Julian Buchrieser; +10 more
    Publisher: Cold Spring Harbor Laboratory
    Country: France
    Project: EC | EVA-GLOBAL (871029)

    A large proportion of SARS-CoV-2 infected individuals remains asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mild and 21 hospitalized COVID-19 patients. We measured anti-Spike IgG, IgA and IgM levels with the S-Flow assay and map IgG-targeted epitopes by Luminex. We also evaluated neutralization, complement deposition and Antibody-Dependent Cellular Cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells. Dufloo et al. show that SARS-CoV-2 infection elicits antibodies that neutralize the virus, activate the complement system and kill infected cells by ADCC. These polyfunctional antibodies are slightly more abundant in symptomatic COVID-19 patients than in asymptomatic individuals and correlate with disease severity. Graphical Abstract

  • Publication . Doctoral thesis . Other literature type . 2019
    Open Access French
    Authors: 
    Joffrin, Léa;
    Publisher: HAL CCSD
    Country: France
    Project: EC | RUN-EMERGE (263958)

    Les zoonoses représentent 60% des maladies infectieuses émergentes, et 70% de ces zoonoses proviennent de la faune sauvage. Les chauves-souris sont les hôtes de nombreux agents infectieux, notamment de virus responsables de zoonoses chez l’Homme comme le virus Ebola, le virus Nipah ou le virus Hendra. Au cours des deux dernières décennies, de nouveaux virus issus des chauves-souris ont émergé dans les populations humaines et animales, avec des conséquences importantes pour la santé publique, vétérinaire, mais également pour l’économie. C’est notamment le cas des coronavirus (CoVs) tels que le syndrome respiratoire aigu sévère (SRAS), le syndrome respiratoire du Moyen-Orient (MERS) et le syndrome de diarrhée aiguë du porc (SADS), responsables de plusieurs milliers de décès humains ainsi que d’une mortalité élevée dans les élevages porcins. Bien que de nombreuses études aient identifié des CoVs de chauves-souris dans le monde, les connaissances actuelles sur la diversité et les risques associés à l'émergence de CoVs dans les écosystèmes insulaires tropicaux restent à évaluer avec précision. L’objectif de cette thèse était d’étudier l’écologie et l’évolution de coronavirus dans des populations de chauves-souris. Dans un premier temps, nous nous sommes intéressés au niveau d’exposition des hôtes aux CoVs, et à l’histoire évolutive de ces virus dans le contexte phylogéographique des îles de l’ouest de l’Océan Indien. Basée sur l’analyse de 1088 échantillons par biologie moléculaire, cette étude a mis en évidence, pour la première fois, la présence de CoV chez des chauves-souris insectivores à Mayotte, au Mozambique, à l’île de La Réunion, et à Madagascar. La prévalence globale de chauves-souris infectées par les CoVs était de 8,0% ± 1,2% avec une variation significative entre l’Afrique continentale et les îles, mais aussi entre familles de chauves-souris. Nous avons identifié une grande diversité génétique de α-CoVs et de β-CoVs, dont certains sont phylogénétiquement proches de CoVs humains (e.g. HCoV-NL63, HCoV-229E, MERS-CoV). Enfin, ces CoVs sont structurés phylogénétiquement par famille de chauves-souris, supportant une longue histoire de coévolution entre chauves-souris et leurs CoVs dans l’Océan Indien occidental. Nous avons dans un second temps réalisé une étude longitudinale sur la dynamique d’infection de CoV dans une colonie de maternité de Petit Molosse (Mormopterus francoismoutoui), espèce endémique de La Réunion. Basé sur la détection du génome viral dans des prélèvements environnementaux (fèces et guano), nous avons exploré l’effet de la structure de la population sur la dynamique d’infection pendant deux années consécutives. Les résultats montrent une variation très marquée des prévalences d’infection chez les chauves-souris au cours de la saison, avec la présence de deux pics d’infection : lors de la colonisation de la grotte de maternité (associé à une augmentation de la densité des hôtes), et environ un mois après le début de la parturition (associé à la perte d’immunité chez les nouveaux-nés). L’ensemble de ces travaux montre que l’évolution des CoVs des chauves-souris de l’ouest de l’Océan Indien est majoritairement due à de la coévolution entre les hôtes et leurs virus, bien que le contexte insulaire puisse également induire de la spéciation intra-île, au sein des familles de chauves-souris. La mise en évidence de facteurs écologiques et biologiques influant sur la dynamique d’infection à l’échelle d’une population souligne que les risques de transmission de CoVs à d’autres hôtes diffèrent en fonction des communautés de chauves-souris présentes sur chaque île, mais aussi de la structure des populations des hôtes et de sa variation temporelle. Zoonoses account for 60% of emerging infectious diseases, among which 70% originate from wildlife. Bats host many infectious agents, including viruses responsible for zoonoses in humans such as Ebola, Nipah or Hendraus. For the last two decades, new bat viruses have emerged in human and animal populations, causing major threats for public and animal health. Coronaviruses (CoV) such as Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and Acute Acute Diarrhea Syndrome (SADS) are responsible for thousands of deaths in humans and pigs. Although many studies have described bat CoVs around the world, current knowledge about the diversity and risks associated with emerging CoVs in island ecosystems remain to be precisely assessed.In this work, we investigated the ecology and evolution of coronaviruses in bats by assessing the level of bat exposure to CoVs, and the evolutionary history in the phylogeographic context of the islands of the Western Indian Ocean. Based on the molecular screening of 1088 samples, we report, for the first time the presence of CoVs in insectivorous bats on Mayotte, on Madagascar, in Mozambique and on Reunion Island. The overall prevalence of bats positive for CoV was 8.0% ± 1.2%, with significant variation between continental Africa and islands, as well as between bat families. We found a large diversity of α-CoVs and β-CoVs, some being genetically related to those detected in human (e.g. HCoV-NL63, HCoV-229E, MERS-CoV). These CoVs were phylogenetically structured by bat family, supporting a long history of co-evolution between bats and their associated CoVs in the region. We then focused on the Reunion free tailed bat (Mormopterus francoismoutoui), an endemic species on this island, and investigated temporal infection dynamics in a maternal colony, during two consecutive years. Results highlighted a major variation in the prevalence of infected bats during the maternity season, with patterns similar for both years and the presence of two peaks of infection. Indeed, one pic occurs during the colonization of the maternity colony (associated to an increase in host density), and another about a month after the beginning of parturition (potentially associated to a loss of maternal antibodies in newborns). This work provides strong support for a long history of coevolution between bats and their CoVs in the Western Indian ocean, although within-island speciation for each bat families also occurs. Ecological and biological factors influencing the infection dynamics highlights a different level of CoV transmission risks to other hosts, including humans, associated to bat communities inhabiting each island, as well as to temporal variations in host population structure.

  • Open Access English
    Authors: 
    Guodong Liang; Xiaoyan Gao; Ernest A. Gould;
    Publisher: HAL CCSD
    Countries: France, United Kingdom
    Project: EC | PREDEMICS (278433), EC | SILVER (260644)

    International audience; Slave trading of Africans to the Americas, during the 16th to the 19th century was responsible for the first recorded emergence in the New World of two arthropod-borne viruses (arboviruses), yellow fever virus and dengue virus. Many other arboviruses have since emerged from their sylvatic reservoirs and dispersed globally due to evolving factors that include anthropological behaviour, commercial transportation and land-remediation. Here, we outline some characteristics of these highly divergent arboviruses, including the variety of life cycles they have developed and the mechanisms by which they have adapted to evolving changes in habitat and host availability. We cite recent examples of virus emergence that exemplify how arboviruses have exploited the consequences of the modern human lifestyle. Using our current understanding of these viruses, we also attempt to demonstrate some of the limitations encountered in developing control strategies to reduce the impact of future emerging arbovirus diseases. Finally, we present recommendations for development by an international panel of experts reporting directly to World Health Organization, with the intention of providing internationally acceptable guidelines for improving emerging arbovirus disease control strategies. Success in these aims should alleviate the suffering and costs encountered during recent decades when arboviruses have emerged from their sylvatic environment.

  • Open Access English
    Authors: 
    Antoine Mandel; Vipin P. Veetil;
    Publisher: Zenodo
    Country: France
    Project: EC | ExSIDE (721846), EC | TIPPING.plus (884565)

    International audience This paper estimates the cost of the lockdown of some sectors of the world economy in the wake of COVID-19. We develop a multi sector disequilibrium model with buyer-seller relations between agents located in different countries. The production network model allows us to study not only the direct cost of the lockdown but also indirect costs which emerge from the reductions in the availability of intermediate inputs. Agents determine the quantity of output and the proportions in which to combine inputs using prices that emerge from local interactions. The model is calibrated to the world economy using input-output data on 56 industries in 44 countries including all major economies. Within our model, the lockdowns are implemented as partial reductions in the output of some sectors using data on sectoral decomposition of capacity reductions. We use computational experiments to replicate the temporal sequence of the lockdowns implemented in different countries. World output falls by 7% at the early stage of the crisis when only China is under lockdown and by 23% at the peak of the crisis when many countries are under a lockdown. These direct impacts are amplified as the shock propagates through the world economy because of the buyer-seller relations. Supply-chain spillovers are capable of amplifying the direct impact by more than two folds. Naturally, the substitutability between intermediate inputs is a major determinant of the amplification. We also study the process of economic recovery following the end of the lockdowns. Price flexibility and minor technological adaptations help in reducing the time it takes for the economy to recover. The world economy takes about one quarter to move towards the new equilibrium in the optimistic and unlikely scenario of the end of all lockdowns. Recovery time is likely to be significantly greater if partial lockdowns persist.

  • English
    Authors: 
    Ivaldi, Serena; Maurice, Pauline; Gomes, Waldez; Theurel, Jean; Wioland, Liên; Atain-Kouadio, Jean-Jacques; Claudon, Laurent; Hani, Hind; Kimmoun, Antoine; Sellal, Jean-Marc; +5 more
    Publisher: HAL CCSD
    Country: France
    Project: EC | An.Dy (731540)
  • Open Access English
    Authors: 
    Pei-Shi Yen; Chun-Hong Chen; Vattipally B. Sreenu; Alain Kohl; Anna-Bella Failloux;
    Publisher: HAL CCSD
    Countries: France, United Kingdom
    Project: EC | ZIKAlliance (734548)

    International audience; Although the role of exogenous small interfering RNA (siRNA) and P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) pathways in mosquito antiviral immunity is increasingly better understood, there is still little knowledge regarding the role of mosquito cellular microRNA (miRNA). Identifying direct interactions between the mosquito miRNAs and the RNA genome of arboviruses and choosing the relevant miRNA candidates to explore resulting antiviral mechanisms are critical. Here, we carried out genomic analyses to identify Aedes aegypti miRNAs that potentially interact with various lineages and genotypes of chikungunya, dengue, and Zika viruses. By using prediction tools with distinct algorithms, several miRNA binding sites were commonly found within different genotypes/and or lineages of each arbovirus. We further analyzed those miRNAs that could target more than one arbovirus, required a low energy threshold to form miRNA-viralRNA (vRNA) complexes, and predicted potential RNA structures using RNAhybrid software. We predicted miRNA candidates that might participate in regulating arboviral replication in Ae. aegypti. Even without any experimental validation, which should be done as a next step, this study can shed further light on the role of miRNA in mosquito innate immunity and targets for future studies.

Advanced search in Research products
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The following results are related to COVID-19. Are you interested to view more results? Visit OpenAIRE - Explore.
321 Research products, page 1 of 33
  • Open Access English
    Authors: 
    Giuliano Bobba; Nicolas Hubé;
    Publisher: Springer International Publishing
    Countries: France, Italy, France
    Project: EC | DEMOS (822590)

    This chapter addresses the general research questions of the book, namely the possibility that populists in Europe can profit from a peculiar crisis such as COVID-19, and it wonders whether populists reacted in a similar way across countries or whether the institutional role they play at the national level has affected their reactions. Findings show that while populists have tried to take advantage of the crisis situation, the impossibility of taking ownership of the COVID-19 issue has made the crisis hard to be exploited. In particular, populists in power have tried to depoliticize the pandemic, whereas radical right-populists in opposition tried to politicize the crisis without gaining relevant public support though.

  • Open Access English
    Authors: 
    Damien Levard; Izaskun Buendia; Anastasia Lanquetin; Martina Glavan; Denis Vivien; Marina Rubio;
    Publisher: Elsevier BV
    Country: France
    Project: EC | ENTRAIN (813294)

    For the last two decades, researchers have placed hopes in a new era in which a combination of reperfusion and neuroprotection would revolutionize the treatment of stroke. Nevertheless, despite the thousands of papers available in the literature showing positive results in preclinical stroke models, randomized clinical trials have failed to show efficacy. It seems clear now that the existing data obtained in preclinical research have depicted an incomplete picture of stroke pathophysiology. In order to ameliorate bench-to-bed translation, in this review we first describe the main actors on stroke inflammatory and immune responses based on the available preclinical data, highlighting the fact that the link between leukocyte infiltration, lesion volume and neurological outcome remains unclear. We then describe what is known on neuroinflammation and immune responses in stroke patients, and summarize the results of the clinical trials on immunomodulatory drugs. In order to understand the gap between clinical trials and preclinical results on stroke, we discuss in detail the experimental results that served as the basis for the summarized clinical trials on immunomodulatory drugs, focusing on (i) experimental stroke models, (ii) the timing and selection of outcome measuring, (iii) alternative entry routes for leukocytes into the ischemic region, and (iv) factors affecting stroke outcome such as gender differences, ageing, comorbidities like hypertension and diabetes, obesity, tobacco, alcohol consumption and previous infections like Covid-19. We can do better for stroke treatment, especially when targeting inflammation following stroke. We need to re-think the design of stroke experimental setups, notably by (i) using clinically relevant models of stroke, (ii) including both radiological and neurological outcomes, (iii) performing long-term follow-up studies, (iv) conducting large-scale preclinical stroke trials, and (v) including stroke comorbidities in preclinical research. Highlights • The different experimental approaches may model different aspects of stroke. • Drugs need to be tested in several clinically relevant experimental stroke models. • Clot composition, type of arterial occlusion and recanalization need to be considered. • Outcomes should include acute but also long-term measurements. • Both infarct volume and behavioral deficits need to be systematically measured. • Including coexisting risk factors in preclinical stroke research is mandatory. • Performing multicenter studies may increase the reliability of preclinical results.

  • Open Access English
    Authors: 
    Laura Di Domenico; Giulia Pullano; Chiara E. Sabbatini; Pierre-Yves Boëlle; Vittoria Colizza;
    Publisher: HAL CCSD
    Country: France
    Project: ANR | DataRedux (ANR-19-CE46-0008), ANR | SPHINx (ANR-17-CE36-0008), EC | MOOD (874850)

    As countries in Europe implement strategies to control the COVID-19 pandemic, different options are chosen regarding schools. Through a stochastic age-structured transmission model calibrated to the observed epidemic in Île-de-France in the first wave, we explored scenarios of partial, progressive, or full school reopening. Given the uncertainty on children’s role, we found that reopening schools after lockdown may increase COVID-19 cases, yet protocols exist to keep the epidemic controlled. Under a scenario with stable epidemic activity if schools were closed, reopening pre-schools and primary schools would lead to up to 76% [67, 84]% occupation of ICU beds if no other school level reopened, or if middle and high schools reopened later. Immediately reopening all school levels may overwhelm the ICU system. Priority should be given to pre- and primary schools allowing younger children to resume learning and development, whereas full attendance in middle and high schools is not recommended for stable or increasing epidemic activity. Large-scale test and trace is required to keep the epidemic under control. Ex-post assessment shows that progressive reopening of schools, limited attendance, and strong adoption of preventive measures contributed to a decreasing epidemic after lifting the first lockdown. The role of children in the spread of COVID-19 is not fully understood, and the circumstances under which schools should be opened are therefore debated. Here, the authors demonstrate protocols by which schools in France can be safely opened without overwhelming the healthcare system.

  • Open Access English
    Authors: 
    Camille Aubry; Sinéad C. Corr; Sebastian Wienerroither; Céline Goulard; Ruth Jones; Amanda M. Jamieson; Thomas Decker; Luke A. J. O'Neill; Olivier Dussurget; Pascale Cossart;
    Publisher: HAL CCSD
    Countries: France, Austria
    Project: EC | MODELIST (233348), FWF | Type I interferons in inn... (P 20522)

    International audience; Synthesis of interferon-beta (IFN-beta) is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-beta synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-beta production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, Delta pgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-beta gene, requiring TLR2 and bacterial internalization. Induction of IFN-beta was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-beta gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-beta gene expression.

  • Open Access
    Authors: 
    Jérémy Dufloo; Ludivine Grzelak; Isabelle Staropoli; Yoann Madec; Laura Tondeur; François Anna; Stéphane Pelleau; Aurélie Wiedemann; Cyril Planchais; Julian Buchrieser; +10 more
    Publisher: Cold Spring Harbor Laboratory
    Country: France
    Project: EC | EVA-GLOBAL (871029)

    A large proportion of SARS-CoV-2 infected individuals remains asymptomatic. Little is known about the extent and quality of their antiviral humoral response. Here, we analyze antibody functions in 52 asymptomatic infected individuals, 119 mild and 21 hospitalized COVID-19 patients. We measured anti-Spike IgG, IgA and IgM levels with the S-Flow assay and map IgG-targeted epitopes by Luminex. We also evaluated neutralization, complement deposition and Antibody-Dependent Cellular Cytotoxicity (ADCC) using replication-competent SARS-CoV-2 or reporter cell systems. We show that COVID-19 sera mediate complement deposition and kill infected cells by ADCC. Sera from asymptomatic individuals neutralize the virus, activate ADCC and trigger complement deposition. Antibody levels and functions are lower in asymptomatic individuals than in symptomatic cases. Antibody functions are correlated, regardless of disease severity. Longitudinal samplings show that antibody functions follow similar kinetics of induction and contraction. Overall, asymptomatic SARS-CoV-2 infection elicits polyfunctional antibodies neutralizing the virus and targeting infected cells. Dufloo et al. show that SARS-CoV-2 infection elicits antibodies that neutralize the virus, activate the complement system and kill infected cells by ADCC. These polyfunctional antibodies are slightly more abundant in symptomatic COVID-19 patients than in asymptomatic individuals and correlate with disease severity. Graphical Abstract

  • Publication . Doctoral thesis . Other literature type . 2019
    Open Access French
    Authors: 
    Joffrin, Léa;
    Publisher: HAL CCSD
    Country: France
    Project: EC | RUN-EMERGE (263958)

    Les zoonoses représentent 60% des maladies infectieuses émergentes, et 70% de ces zoonoses proviennent de la faune sauvage. Les chauves-souris sont les hôtes de nombreux agents infectieux, notamment de virus responsables de zoonoses chez l’Homme comme le virus Ebola, le virus Nipah ou le virus Hendra. Au cours des deux dernières décennies, de nouveaux virus issus des chauves-souris ont émergé dans les populations humaines et animales, avec des conséquences importantes pour la santé publique, vétérinaire, mais également pour l’économie. C’est notamment le cas des coronavirus (CoVs) tels que le syndrome respiratoire aigu sévère (SRAS), le syndrome respiratoire du Moyen-Orient (MERS) et le syndrome de diarrhée aiguë du porc (SADS), responsables de plusieurs milliers de décès humains ainsi que d’une mortalité élevée dans les élevages porcins. Bien que de nombreuses études aient identifié des CoVs de chauves-souris dans le monde, les connaissances actuelles sur la diversité et les risques associés à l'émergence de CoVs dans les écosystèmes insulaires tropicaux restent à évaluer avec précision. L’objectif de cette thèse était d’étudier l’écologie et l’évolution de coronavirus dans des populations de chauves-souris. Dans un premier temps, nous nous sommes intéressés au niveau d’exposition des hôtes aux CoVs, et à l’histoire évolutive de ces virus dans le contexte phylogéographique des îles de l’ouest de l’Océan Indien. Basée sur l’analyse de 1088 échantillons par biologie moléculaire, cette étude a mis en évidence, pour la première fois, la présence de CoV chez des chauves-souris insectivores à Mayotte, au Mozambique, à l’île de La Réunion, et à Madagascar. La prévalence globale de chauves-souris infectées par les CoVs était de 8,0% ± 1,2% avec une variation significative entre l’Afrique continentale et les îles, mais aussi entre familles de chauves-souris. Nous avons identifié une grande diversité génétique de α-CoVs et de β-CoVs, dont certains sont phylogénétiquement proches de CoVs humains (e.g. HCoV-NL63, HCoV-229E, MERS-CoV). Enfin, ces CoVs sont structurés phylogénétiquement par famille de chauves-souris, supportant une longue histoire de coévolution entre chauves-souris et leurs CoVs dans l’Océan Indien occidental. Nous avons dans un second temps réalisé une étude longitudinale sur la dynamique d’infection de CoV dans une colonie de maternité de Petit Molosse (Mormopterus francoismoutoui), espèce endémique de La Réunion. Basé sur la détection du génome viral dans des prélèvements environnementaux (fèces et guano), nous avons exploré l’effet de la structure de la population sur la dynamique d’infection pendant deux années consécutives. Les résultats montrent une variation très marquée des prévalences d’infection chez les chauves-souris au cours de la saison, avec la présence de deux pics d’infection : lors de la colonisation de la grotte de maternité (associé à une augmentation de la densité des hôtes), et environ un mois après le début de la parturition (associé à la perte d’immunité chez les nouveaux-nés). L’ensemble de ces travaux montre que l’évolution des CoVs des chauves-souris de l’ouest de l’Océan Indien est majoritairement due à de la coévolution entre les hôtes et leurs virus, bien que le contexte insulaire puisse également induire de la spéciation intra-île, au sein des familles de chauves-souris. La mise en évidence de facteurs écologiques et biologiques influant sur la dynamique d’infection à l’échelle d’une population souligne que les risques de transmission de CoVs à d’autres hôtes diffèrent en fonction des communautés de chauves-souris présentes sur chaque île, mais aussi de la structure des populations des hôtes et de sa variation temporelle. Zoonoses account for 60% of emerging infectious diseases, among which 70% originate from wildlife. Bats host many infectious agents, including viruses responsible for zoonoses in humans such as Ebola, Nipah or Hendraus. For the last two decades, new bat viruses have emerged in human and animal populations, causing major threats for public and animal health. Coronaviruses (CoV) such as Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS) and Acute Acute Diarrhea Syndrome (SADS) are responsible for thousands of deaths in humans and pigs. Although many studies have described bat CoVs around the world, current knowledge about the diversity and risks associated with emerging CoVs in island ecosystems remain to be precisely assessed.In this work, we investigated the ecology and evolution of coronaviruses in bats by assessing the level of bat exposure to CoVs, and the evolutionary history in the phylogeographic context of the islands of the Western Indian Ocean. Based on the molecular screening of 1088 samples, we report, for the first time the presence of CoVs in insectivorous bats on Mayotte, on Madagascar, in Mozambique and on Reunion Island. The overall prevalence of bats positive for CoV was 8.0% ± 1.2%, with significant variation between continental Africa and islands, as well as between bat families. We found a large diversity of α-CoVs and β-CoVs, some being genetically related to those detected in human (e.g. HCoV-NL63, HCoV-229E, MERS-CoV). These CoVs were phylogenetically structured by bat family, supporting a long history of co-evolution between bats and their associated CoVs in the region. We then focused on the Reunion free tailed bat (Mormopterus francoismoutoui), an endemic species on this island, and investigated temporal infection dynamics in a maternal colony, during two consecutive years. Results highlighted a major variation in the prevalence of infected bats during the maternity season, with patterns similar for both years and the presence of two peaks of infection. Indeed, one pic occurs during the colonization of the maternity colony (associated to an increase in host density), and another about a month after the beginning of parturition (potentially associated to a loss of maternal antibodies in newborns). This work provides strong support for a long history of coevolution between bats and their CoVs in the Western Indian ocean, although within-island speciation for each bat families also occurs. Ecological and biological factors influencing the infection dynamics highlights a different level of CoV transmission risks to other hosts, including humans, associated to bat communities inhabiting each island, as well as to temporal variations in host population structure.

  • Open Access English
    Authors: 
    Guodong Liang; Xiaoyan Gao; Ernest A. Gould;
    Publisher: HAL CCSD
    Countries: France, United Kingdom
    Project: EC | PREDEMICS (278433), EC | SILVER (260644)

    International audience; Slave trading of Africans to the Americas, during the 16th to the 19th century was responsible for the first recorded emergence in the New World of two arthropod-borne viruses (arboviruses), yellow fever virus and dengue virus. Many other arboviruses have since emerged from their sylvatic reservoirs and dispersed globally due to evolving factors that include anthropological behaviour, commercial transportation and land-remediation. Here, we outline some characteristics of these highly divergent arboviruses, including the variety of life cycles they have developed and the mechanisms by which they have adapted to evolving changes in habitat and host availability. We cite recent examples of virus emergence that exemplify how arboviruses have exploited the consequences of the modern human lifestyle. Using our current understanding of these viruses, we also attempt to demonstrate some of the limitations encountered in developing control strategies to reduce the impact of future emerging arbovirus diseases. Finally, we present recommendations for development by an international panel of experts reporting directly to World Health Organization, with the intention of providing internationally acceptable guidelines for improving emerging arbovirus disease control strategies. Success in these aims should alleviate the suffering and costs encountered during recent decades when arboviruses have emerged from their sylvatic environment.

  • Open Access English
    Authors: 
    Antoine Mandel; Vipin P. Veetil;
    Publisher: Zenodo
    Country: France
    Project: EC | ExSIDE (721846), EC | TIPPING.plus (884565)

    International audience This paper estimates the cost of the lockdown of some sectors of the world economy in the wake of COVID-19. We develop a multi sector disequilibrium model with buyer-seller relations between agents located in different countries. The production network model allows us to study not only the direct cost of the lockdown but also indirect costs which emerge from the reductions in the availability of intermediate inputs. Agents determine the quantity of output and the proportions in which to combine inputs using prices that emerge from local interactions. The model is calibrated to the world economy using input-output data on 56 industries in 44 countries including all major economies. Within our model, the lockdowns are implemented as partial reductions in the output of some sectors using data on sectoral decomposition of capacity reductions. We use computational experiments to replicate the temporal sequence of the lockdowns implemented in different countries. World output falls by 7% at the early stage of the crisis when only China is under lockdown and by 23% at the peak of the crisis when many countries are under a lockdown. These direct impacts are amplified as the shock propagates through the world economy because of the buyer-seller relations. Supply-chain spillovers are capable of amplifying the direct impact by more than two folds. Naturally, the substitutability between intermediate inputs is a major determinant of the amplification. We also study the process of economic recovery following the end of the lockdowns. Price flexibility and minor technological adaptations help in reducing the time it takes for the economy to recover. The world economy takes about one quarter to move towards the new equilibrium in the optimistic and unlikely scenario of the end of all lockdowns. Recovery time is likely to be significantly greater if partial lockdowns persist.

  • English
    Authors: 
    Ivaldi, Serena; Maurice, Pauline; Gomes, Waldez; Theurel, Jean; Wioland, Liên; Atain-Kouadio, Jean-Jacques; Claudon, Laurent; Hani, Hind; Kimmoun, Antoine; Sellal, Jean-Marc; +5 more
    Publisher: HAL CCSD
    Country: France
    Project: EC | An.Dy (731540)
  • Open Access English
    Authors: 
    Pei-Shi Yen; Chun-Hong Chen; Vattipally B. Sreenu; Alain Kohl; Anna-Bella Failloux;
    Publisher: HAL CCSD
    Countries: France, United Kingdom
    Project: EC | ZIKAlliance (734548)

    International audience; Although the role of exogenous small interfering RNA (siRNA) and P-element induced wimpy testis (PIWI)-interacting RNA (piRNA) pathways in mosquito antiviral immunity is increasingly better understood, there is still little knowledge regarding the role of mosquito cellular microRNA (miRNA). Identifying direct interactions between the mosquito miRNAs and the RNA genome of arboviruses and choosing the relevant miRNA candidates to explore resulting antiviral mechanisms are critical. Here, we carried out genomic analyses to identify Aedes aegypti miRNAs that potentially interact with various lineages and genotypes of chikungunya, dengue, and Zika viruses. By using prediction tools with distinct algorithms, several miRNA binding sites were commonly found within different genotypes/and or lineages of each arbovirus. We further analyzed those miRNAs that could target more than one arbovirus, required a low energy threshold to form miRNA-viralRNA (vRNA) complexes, and predicted potential RNA structures using RNAhybrid software. We predicted miRNA candidates that might participate in regulating arboviral replication in Ae. aegypti. Even without any experimental validation, which should be done as a next step, this study can shed further light on the role of miRNA in mosquito innate immunity and targets for future studies.