Philippe JEAN-PIERRE

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• Type de publi. : Article dans une revue
• Date de publi. : 22/04/2021
• Auteurs : Hiroki MizuochiAgnes DucharneFrederique CheruyJosefine GhattasAmen Al-YaariWigneron J.-P.P. PeylinFabienne MaignanN. Vuichard
• Organismes : National Institute of Advanced Industrial Science and Technology Milieux Environnementaux, Transferts et Interactions dans les hydrosystèmes et les Sols Laboratoire de Météorologie Dynamique (UMR 8539) Institut Pierre-Simon-Laplace
• Publié dans Hydrology and Earth System Sciences le 24/10/2020

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Résumé : Abstract. Evaluating land surface models (LSMs) using available observations is important to understand the potential and limitations of current Earth system models in simulating water- and carbon-related variables. To reveal the error sources of a land surface model (LSM), four essential climate variables have been evaluated in this paper (i.e., surface soil moisture, evapotranspiration, leaf area index, and surface albedo) via simulations with IPSL LSM ORCHIDEE (Organizing Carbon and Hydrology in Dynamic Ecosystems), particularly focusing on the difference between (i) forced simulations with atmospheric forcing data (WATCH-Forcing-DATA-ERA-Interim: WFDEI) and (ii) coupled simulations with the IPSL atmospheric general circulation model. Results from statistical evaluation using satellite- and ground-based reference data show that ORCHIDEE is well equipped to represent spatiotemporal patterns of all variables in general. However, further analysis against various landscape/meteorological factors (e.g., plant functional type, slope, precipitation, and irrigation) suggests potential uncertainty relating to freezing/snowmelt, temperate plant phenology, irrigation, as well as contrasted responses between forced and coupled mode simulations. The biases in the simulated variables are amplified in coupled mode via surface–atmosphere interactions, indicating a strong link between irrigation–precipitation and a relatively complex link between precipitation–evapotranspiration that reflects the hydrometeorological regime of the region (energy-limited or water-limited) and snow-albedo feedback in mountainous and boreal regions. The different results between forced and coupled modes imply the importance of model evaluation under both modes to isolate potential sources of uncertainty in the model.

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Fichiers liés : hess-2020-438.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 22/04/2021
• Auteurs : Jean QuertinmontPierre BeaujeanJulien StiennonYoussef AidibiPhilippe LericheVincent RodriguezLionel SanguinetBenoît Champagne
• Organismes : MOLTECH-Anjou MOLTECH-Anjou MOLTECH-Anjou
• Publié dans Journal of Physical Chemistry B le 22/10/2020

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• Type de publi. : Article dans une revue
• Date de publi. : 20/04/2021
• Auteurs : Hui YangPhilippe CiaisE. Vilella FiguerasYuanyuan HuangWigneron J.-P.Ana BastosJérôme ChaveJinfeng ChangChristopher DoughtySassan S SaatchiDaniel S GollEmilie JoetzjerWei LiRichard LucasShaun QueganThuy Le ToanKailiang Yu
• Organismes : Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] ICOS-ATC Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Interactions Sol Plante Atmosphère Max Planck Institute for Biogeochemistry Université Toulouse III - Paul Sabatier Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Northern Arizona University [Flagstaff] Interactions Sol Plante Atmosphère Universität Augsburg [Deutschland] = University of Augsburg [Germany] = Université d'Augsbourg [Allemagne] Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] Contrôles des cycles biogéochimiques terrestres Centre national de recherches météorologiques Tsinghua University [Beijing] Aberystwyth University University of Sheffield [Sheffield] Centre d'études spatiales de la biosphère Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette]
• Publié dans Global Ecology and Biogeography le 25/10/2020

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Résumé : Aim : The carbon sink in tropical forests is a highly uncertain component of the global carbon budget. An understanding of the processes controlling this sink requires better quantification of carbon allocation, stocks and turnover times. Location : Tropical forests. Time period : 2010–2017. Major taxa studied : Tropical forest ecosystem. Methods : We develop a novel data assimilation system using satellite-based annual above-ground biomass derived from L-band vegetation optical depth with 25 km × 25 km grid spacing, together with leaf area, to constrain the 25 km × 25 km carbon allocation patterns of net primary productivity (NPP) into the wood, leaf and root pools, and their turnover times. Our average data-driven estimates of these variables are broadly consistent with independent ground-based estimates of NPP allocation and wood turnover from forest inventory plots. Results : In tropical forest, on average, the NPP allocation into wood (0.30 ± 0.04) is significantly higher than that into leaves (0.24 ± 0.07). From the wet to dry tropics, forest NPP allocation into both wood and leaves declines slightly. The turnover times of forest leaf pools exhibit little spatial variation, whereas the turnover times of wood pools in Africa (median and interquartile range: urn:x-wiley:1466822X:media:geb13302:geb13302-math-0001 years) are slightly longer than those in South America (urn:x-wiley:1466822X:media:geb13302:geb13302-math-0002 years) and Southeast Asia (urn:x-wiley:1466822X:media:geb13302:geb13302-math-0003 years). Our datasets reveal emergent trade-offs across climatic and vegetation gradients between growth and life span/turnover for both wood and leaves. The spatial gradients of NPP allocation to wood/leaves are associated with canopy height, adjusted by climate condition and nutrient acquisition. The spatial gradients of wood and leaf turnover times are influenced mainly by climate and leaf characteristics. Main conclusions : Our data-driven estimates of carbon allocation and turnover times provide a basis for more detailed exploration of these mechanisms in field studies. This highlights that improved model representation of carbon allocation and turnover is necessary for more accurate prediction of future carbon dynamics.

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• Type de publi. : Article dans une revue
• Date de publi. : 20/04/2021
• Auteurs : Antoine YrondiChristophe ArbusDjamila BennabiThierry A. d'AmatoFrank BellivierThierry BougerolVincent CamusPhilippe CourtetOlivier DoumyJean-Baptiste GentyJérôme HoltzmannMathilde HornChristophe LançonMarion LeboyerPierre-Michel LlorcaJulia MaruaniRémi MoirandFanny MolièreJean PetrucciRaphaelle RichieriLudovic SamalinFlorian StephanGuillaume VaivaMichel WalterEmmanuel HaffenBruno AouizerateWissam El-Hage
• Organismes : Toulouse NeuroImaging Center Fondation FondaMental [Créteil] Service Psychiatrie et psychologie médicale [CHU Toulouse] Toulouse NeuroImaging Center Fondation FondaMental [Créteil] Service Psychiatrie et psychologie médicale [CHU Toulouse] Fondation FondaMental [Créteil] Centre d'Investigation Clinique de Besançon Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Fondation FondaMental [Créteil] Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris] Fondation FondaMental [Créteil] [GIN] Grenoble Institut des Neurosciences Fondation FondaMental [Créteil] Imaging, Brain & Neuropsychiatry Fondation FondaMental [Créteil] Centre d’Investigation Clinique [Tours] CIC 1415 Neuropsychiatrie : recherche épidémiologique et clinique Fondation FondaMental [Créteil] Nutrition et Neurobiologie intégrée Fondation FondaMental [Créteil] Institut Mondor de Recherche Biomédicale Fondation FondaMental [Créteil] IMRB - "Neuropsychiatrie translationnelle" [Créteil] Fondation FondaMental [Créteil] [GIN] Grenoble Institut des Neurosciences Fondation FondaMental [Créteil] Centre Hospitalier Régional Universitaire [CHU Lille] Fondation FondaMental [Créteil] Hôpital de la Conception [CHU - APHM] Fondation FondaMental [Créteil] Institut Mondor de Recherche Biomédicale IMRB - "Neuropsychiatrie translationnelle" [Créteil] Fondation FondaMental [Créteil] Service Psychiatrie Adulte [CHU Clermont-Ferrand] Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris] Fondation FondaMental [Créteil] Fondation FondaMental [Créteil] Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center Neuropsychiatrie : recherche épidémiologique et clinique Fondation FondaMental [Créteil] Fondation FondaMental [Créteil] Institut Mondor de Recherche Biomédicale IMRB - "Neuropsychiatrie translationnelle" [Créteil] Hôpital de la Conception [CHU - APHM] Fondation FondaMental [Créteil] Service Psychiatrie Adulte [CHU Clermont-Ferrand] Fondation FondaMental [Créteil] Fondation FondaMental [Créteil] CHRU Brest - Psychiatrie Adulte Fondation FondaMental [Créteil] Centre National de Ressources et de Résilience [Lille] Fondation FondaMental [Créteil] CHRU Brest - Psychiatrie Adulte Fondation FondaMental [Créteil] Centre d'Investigation Clinique de Besançon Nutrition et Neurobiologie intégrée Fondation FondaMental [Créteil] Imaging, Brain & Neuropsychiatry Centre d’Investigation Clinique [Tours] CIC 1415 Fondation FondaMental [Créteil]
• Publié dans PLoS ONE le 25/10/2020

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Résumé : Introduction: We assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample. Methods: Patients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres. Results: Our sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0-60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0-27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0-30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly's Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect. Conclusion: To our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms.

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Fichiers liés : journal.pone.0250148.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 20/04/2021
• Auteurs : Nathalie FaumontOussama TaouiDavi CollaresJean-Philippe JaisKaren LeroyLéa PrévaudFabrice JardinThierry J MolinaChristiane Copie-BergmanBarbara PetitMarie-Pierre GourinDominique BordessouleDanielle TroutaudVéronique BaudJean Feuillard
• Organismes : Contrôle de la Réponse Immune B et des Lymphoproliférations Contrôle de la Réponse Immune B et des Lymphoproliférations Imagine - Institut des maladies génétiques (IHU) Centre de Recherche des Cordeliers Contrôle de la Réponse Immune B et des Lymphoproliférations Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques Hôpital Necker - Enfants Malades [AP-HP] Institut Mondor de Recherche Biomédicale CHU Limoges Service d'Hématologie clinique et thérapie cellulaire [CHU Limoges] Contrôle de la Réponse Immune B et des Lymphoproliférations Contrôle de l’Activation Cellulaire, Progression Tumorale et Résistance thérapeutique Contrôle de la Réponse Immune B et des Lymphoproliférations
• Publié dans Frontiers in Oncology le 26/10/2020

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Résumé : Relationships between c-Rel and GCB-DLBCLs remain unclear. We found that strong c-Rel DNA-binding activity was mostly found in GCBs on two independent series of 48 DLBCLs and 66 DLBCLs, the latter issued from the GHEDI series. c-Rel DNA-binding activity was associated with increased REL mRNA expression. Extending the study to the whole GHEDI and Lenz DLBCL published series of 202 and 233 cases, it was found that the c-Rel gene expression profile (GEP) overlapped partially (12%) but only with the GCB GEP and not with the GEP of ABC-DLBCLs. Cases with both overexpression of REL mRNA and c-Rel GEP were defined as those having a c-Rel signature. These cases were GCBs in 88 and 83% of the GHEDI or Lenz's DLBCL series respectively. The c-Rel signature was also associated with various recurrent GCB-DLBCL genetic events, including REL gains, BCL2 translocation, MEF2B, EZH2, CREBBP, and TNFRSF14 mutations and with the EZB GCB genetic subtype. By CGH array, the c-Rel signature was specifically correlated with 2p15-16.1 amplification that includes XPO1, BCL11A, and USP34 and with the 22q11.22 deletion that covers IGLL5 and PRAME. The total number of gene copy number aberrations, so-called genomic imbalance complexity, was decreased in cases with the c-Rel signature. These cases exhibited a better overall survival. Functionally, overexpression of c-Rel induced its constitutive nuclear localization and protected cells against apoptosis while its repression tended to increase cell death. These results show that, clinically and biologically, c-Rel is the pivotal NF-κB subunit in the GCB-DLBCL subgroup. Functionally, c-Rel overexpression could directly promote DLBCL tumorigenesis without need for further activation signals.

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Fichiers liés : fonc-11-638897.pdf

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• Type de publi. :
• Date de publi. : 19/04/2021
• Auteurs : Crelia PadronFrauke KlingelhoeferB. MarcaillouJean-Frédéric LebrunSerge LallemandGarrocq ClementMireille LaigleWalter RoestMarie-Odile BeslierLaure ScheniniDavid GraindorgeAurélien GayFranck AudemardPhilippe Munch
• Organismes : Institut Français de Recherche pour l'Exploitation de la Mer Institut Français de Recherche pour l'Exploitation de la Mer Geo-Ocean Géoazur Géosciences Montpellier Géosciences Montpellier Université des Antilles Géosciences Montpellier Université des Antilles Géoazur Unité Géosciences Marines Géoazur Géoazur Geo-Ocean Géosciences Montpellier Fundación Venezolana de Investigaciones Sismológicas Géosciences Montpellier

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Résumé : Studying back-arc basins, where sedimentation is less deformed than in the forearc, provides complementary information about formation and tectonic evolution of subduction zones. At the Lesser Antilles subduction zone, the North and South American plates are subducting underneath the Caribbean plate at a velocity of 2 cm per year. The crescent-shaped Grenada back-arc basin is located between the Aves Ridge, which hosted the remnant Early Paleogene “Great Caribbean Arc”, and the Eocene to present Lesser Antilles Arc. In this study, based on wide-angle data, we provide constraints about lateral variations in basement thickness and velocity structure in the Lesser Antilles back-arc, and to a lesser extend in the arc and forearc domain, constraining for the first time the extent of oceanic crust in the Grenada Basin and shed light on the structure and compositions of the basin’s margins. Three combined wide-angle and reflection seismic profiles, together with gravity and bathymetric data, were acquired in the Lesser Antilles back-arc basin. Direct modeling techniques were applied to the wide-angle seismic data in order to include shallow structures imaged by the coincident reflection seismic data. The resulting velocity models were additionally constrained by gravity modeling and synthetic seismogram calculation. The final models from direct modeling image variations in thickness and velocity structure of the sedimentary and crustal layers to a depth of up to 35 km. The sedimentary cover has a variable thickness from less than a kilometer on top of the ridges to nearly 10 km in the basin. North of Guadeloupe Island, the crust is ~20 km thick from back-arc to forearc, without significant change between the Aves Ridge, the Eocene and present Lesser Antilles volcanic arc. While based on the seismic velocities, the southern part of the basin is underlain by a 6.5-7 km thick crust of of mainly magmatic origin over a width of ~80 km, the northern part is underlain by thinned continental crust. At the western flank of the Lesser Antilles Arc, the crust is 17.5-km thick, about 5 km thinner than north of Martinique island. The velocity structure is typical of volcanic arcs or oceanic plateaus. Between Aves Ridge and the Grenada basin the crust thins in a 80-100 km wide transition zone. No anomalous high velocities indicating the presence of exhumed upper mantle material were detected at the transition zone. This narrow E-W arc-ocean transition zone suggests that opening might have proceeded in a direction highly oblique to the main convergence.

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• Type de publi. : Communication dans un congrès
• Date de publi. : 19/04/2021
• Auteurs : Mathilde BanjanChristian CrouzetPierre SabatierHervé JomardFrançois DemoryAnne-Lise DevelleJean-Philippe JennyNathaniel FindlingPhilippe AlainErwan Messager
• Organismes : Centre Européen de Recherche et d'Enseignement des Géosciences de l'Environnement

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Résumé : <p>Seismic hazard calculations are based on the assumption that seismicity rates are stable over time. In a given area, the seismicity recorded through historical archives and seismometers is considered a reliable indicator to model the occurrence of future high magnitude seismic events. But, to discuss this hypothesis regionally, it is essential to reconstruct long term seismicity.</p><p>The junction between the Jura mountains and the Alps is seismically active, as shown by the occurrence of numerous seismic events and the presence of several active faults (De La Taille, 2015). Since the 15^thcentury, more than twenty earthquakes of epicentral intensity greater than VII have been identified in this area. In addition, sedimentary sequences from Lake Annecy and Lake du Bourget have highlighted the capacity of these "natural archives" to record recurrent seismic activity (Beck 2009), with a potential major seismic event identified around 9900 cal. BP (Arnaud et al., 2012). Such lacustrine archives are key to better understand 1) the occurrence of major seismic events and 2) the evolution of seismicity rates through time, prior to historical and instrumental records.</p><p>Here, we present two sedimentary sequences of 11 and 16 metres long respectively, sampled in the shallowest and deepest basins of Lake Aiguebelette (altitude: 374 m). We performed sedimentological, geochemical and paleomagnetic analyses combined with seismic profile analyses and radiocarbon dating to study processes of event layer deposition in this lake. Multi-proxy analyses allow a quantitative identification of event layers, contrasting with varved-sedimentation. In the deepest basin sequence, 33 homogenites are identified through variations of the laboratory induced isothermal remanent magnetization of sediments measured with a high-resolution fluxgate scanner (Demory et al., 2019) and high foliation (>2%) of the Anisotropy of Magnetic Susceptibility. These parameters are usually associated with seiche effect induced by seismic activity (Campos et al., 2013). Among these event layers, archived in the deep basin sequence, three of them occured synchronously in the shallow basin (at 3000 &#177; 100, 6900 &#177; 100 and 11400 &#177; 300 cal. BP, respectively).</p><p>The oldest and thickest event layer recorded in Lake Aiguebelette was deposited at the transition between the Late Glacial and Holocene stages. In the deepest basin, this 1.15-meter-thick deposit is composed of an upward-graded base and a 0.84 meter-thick homogenite, which was also identified as a transparent facies on seismic profiles. In Lake Le Bourget, Lake Annecy, and central Swiss perialpine lakes, several seismic profiles analyses show transparent seismic facies interpreted as mass movement deposits occurring at the same period of time: the Late glacial-Holocene transition.</p><p>Did this climatic transition influence the seismic activity in the Alps? If so, the impact of such climatic forcing on seismic hazard assessment should be evaluated.</p><p>&#160;</p><p>Arnaud et al (2012). Lake Bourget regional erosion patterns... QSR., 51, 81-92.</p><p>Beck (2009). Late Quaternary lacustrine paleo-seismic... EarthSciRev., 96(4), 327-344.</p><p>Campos et al (2013). Deciphering hemipelagites from homogenites... SedGeol., 292, 1-14.</p><p>De La Taille et al (2015). Impact of active faulting... Tectonophysics, 664, 31-49.</p><p>Demory et al (2019). A new high&#8208;resolution magnetic scanner... Geochem,Geophy,Geosys., 20(7), 3186-3200.</p><p>&#160;</p><p><strong>Keywords: </strong>Lake sediment, homogenites, paleo-earthquakes, seismic hazard, French Alps</p><p>&#160;</p><p>&#160;</p>

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• Type de publi. : Communication dans un congrès
• Date de publi. : 19/04/2021
• Auteurs : Déborah HarletGuilhem Amin DouilletJean-François GhienneChloé BouscaryPhilippe RazinPierre DietrichFritz Schlunegger
• Organismes : Universität Bern = University of Bern = Université de Berne Ecole et Observatoire des Sciences de la Terre Ecole et Observatoire des Sciences de la Terre Institut des Dynamiques de la Surface Terrestre [Lausanne] École Nationale Supérieure en Environnement, Géoressources et Ingénierie du Développement Durable Géosciences Rennes Universität Bern = University of Bern = Université de Berne

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Résumé : The Moroccan Anti-Atlas consists of a several kilometers thick sediment pile accumulated on the northern Gondwana platform since the latest Precambrian (Ediacaran). This study focuses on the Ktaoua Group, early Late Ordovician (Mid-Sandbian to Katian) in age, which records a major and multiphase transgressive/regressive cycle above the shallow marine sandstones of the underlying First Bani Group. In the western Central Anti-Atlas, the Ktaoua Group is formed by offshore shales to coastal sandstones organized in regressive parasequences. Here, high-resolution field-based stratigraphy is used to constrain the shelf architecture and clinoforms geometries within the Ktaoua Group.</span></span></p><p><span><span>Whereas the lower part of the Ktaoua Group records parasequences from silty-shale to fine to coarse sandstones with hummocky-cross-stratification (HCS), its upper part oscillates between HCS beds and very coarse sandstones. Ferruginous, condensed horizons usually drape the parasequences. In this study, we investigate the platform geometry through the correlation of the stacking patterns of seventeen stratigraphic logs along an 85 km long, well-exposed cliff. Drone images support the logging and the correlations of the sections by imaging clinoforms geometries. Several decameters of fine to coarse sandstones can be observed to grade laterally into condensed level(s) within a few kilometers, hence evidencing clinoforms pinching out. The visible orientation of the clinoforms along the cliff exposures show a proximal to distal trend from the south-west to the north-east, in agreement with the overall basin geometry. Three clinoforms with distinct geometries and lateral evolution of facies associations are highlighted. The distal part of a clinoform, 15 m in thickness, pinches out onto the top of the underlying First Bani Group within 7 km. The overlying regressive parasequence, approximatively 50 m thick, remains consistent more than 50 km, and is understood as a prograding clinoform. A third clinoform, capped by a prominent sandstone body constantly thicker than 20 m over ca. 20 km, disappears within its last 3.5 km onto the underlying clinoform. This study offers new details on the progradation and regression geometries along a giant platform within a detailed stratigraphic framework. We would like to thank the Pacha and the Gendarmerie Royale of Foum-Zguid, the governor of Tata and the different persons who gave their approval and facilitated the use of the drone in the region of Souss-Massa for their precious help.

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• Type de publi. : Article dans une revue
• Date de publi. : 19/04/2021
• Auteurs : Marie Armani-TourretZhicheng ZhouRomain GasserIsabelle StaropoliVincent Cantaloube-FerrieuYann BenureauJavier Garcia-PerezMayte Pérez-OlmedaValérie LorinBénédicte Puissant-LubranoLambert AssoumouConstance DelaugerreJean-Daniel LelièvreYves LévyHugo MouquetGuillaume Martin-BlondelJose AlcamiFernando Arenzana-SeisdedosJacques IzopetPhilippe ColinBernard Lagane
• Organismes : Institut Toulousain des Maladies Infectieuses et Inflammatoires Pathogénie Virale - Viral Pathogenesis Institut Toulousain des Maladies Infectieuses et Inflammatoires Pathogénie Virale - Viral Pathogenesis Institut Toulousain des Maladies Infectieuses et Inflammatoires Pathogénie Virale - Viral Pathogenesis Instituto de Salud Carlos III [Madrid] Instituto de Salud Carlos III [Madrid] Immunologie humorale - Humoral Immunology Institut Toulousain des Maladies Infectieuses et Inflammatoires Institut Pierre Louis d'Epidémiologie et de Santé Publique Génomes, biologie cellulaire et thérapeutiques CHU Henri Mondor [Créteil] CHU Henri Mondor [Créteil] Immunologie humorale - Humoral Immunology Institut Toulousain des Maladies Infectieuses et Inflammatoires Service Maladies infectieuses et tropicales [CHU Toulouse] Instituto de Salud Carlos III [Madrid] Pathogénie Virale - Viral Pathogenesis Institut Toulousain des Maladies Infectieuses et Inflammatoires Laboratoire Virologie [CHU Toulouse] Institut Toulousain des Maladies Infectieuses et Inflammatoires Institut Toulousain des Maladies Infectieuses et Inflammatoires
• Publié dans PLoS Pathogens le 27/10/2020

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Résumé : HIV-1 infects CD4 T lymphocytes (CD4TL) through binding the chemokine receptors CCR5 or CXCR4. CXCR4-using viruses are considered more pathogenic, linked to accelerated depletion of CD4TL and progression to AIDS. However, counterexamples to this paradigm are common, suggesting heterogeneity in the virulence of CXCR4-using viruses. Here, we investigated the role of the CXCR4 chemokine CXCL12 as a driving force behind virus virulence. In vitro, CXCL12 prevents HIV-1 from binding CXCR4 and entering CD4TL, but its role in HIV-1 transmission and propagation remains speculative. Through analysis of thirty envelope glycoproteins (Envs) from patients at different stages of infection, mostly treatment-naïve, we first interrogated whether sensitivity of viruses to inhibition by CXCL12 varies over time in infection. Results show that Envs resistant (RES) to CXCL12 are frequent in patients experiencing low CD4TL levels, most often late in infection, only rarely at the time of primary infection. Sensitivity assays to soluble CD4 or broadly neutralizing antibodies further showed that RES Envs adopt a more closed conformation with distinct antigenicity, compared to CXCL12-sensitive (SENS) Envs. At the level of the host cell, our results suggest that resistance is not due to improved fusion or binding to CD4, but owes to viruses using particular CXCR4 molecules weakly accessible to CXCL12. We finally asked whether the low CD4TL levels in patients are related to increased pathogenicity of RES viruses. Resistance actually provides viruses with an enhanced capacity to enter naive CD4TL when surrounded by CXCL12, which mirrors their situation in lymphoid organs, and to deplete bystander activated effector memory cells. Therefore, RES viruses seem more likely to deregulate CD4TL homeostasis. This work improves our understanding of the pathophysiology and the transmission of HIV-1 and suggests that RES viruses' receptors could represent new therapeutic targets to help prevent CD4TL depletion in HIV+ patients on cART.

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Fichiers liés : journal.ppat.1009526.pdf

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• Type de publi. : Communication dans un congrès
• Date de publi. : 17/04/2021
• Auteurs : Christophe LucchesiDilek CakirogluJean-Philippe PerezThierry TaliercioEric TourniéPierre-Olivier ChapuisRodolphe Vaillon
• Organismes : Centre d'Energétique et de Thermique de Lyon Composants à Nanostructure pour le moyen infrarouge Institut d’Electronique et des Systèmes Composants à Nanostructure pour le moyen infrarouge Institut d’Electronique et des Systèmes Composants à Nanostructure pour le moyen infrarouge Institut d’Electronique et des Systèmes Composants à Nanostructure pour le moyen infrarouge Institut d’Electronique et des Systèmes Centre d'Energétique et de Thermique de Lyon Micro électronique, Composants, Systèmes, Efficacité Energétique Institut d’Electronique et des Systèmes

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