Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses

We demonstrated previously that the cytosine deaminase APOBEC3G inhibits retrotransposition of two active murine endogenous retroviruses, namely intracisternal A-particles (IAP) and MusD, in an ex vivo assay where retrotransposition was monitored by selection of neo-marked elements. Sequencing of the transposed copies further disclosed extensive editing, resulting in a high load of G-to-A mutations. Here, we asked whether this G-to-A editing was associated with an impact of APOBEC3G on viral cDNA yields. To this end, we used a specially designed quantitative PCR method to selectively measure the copy number of transposed retroelements, in the absence of G418 selection. We show that human APOBEC3G severely reduces the number of MusD and IAP transposed cDNA copies, with no effect on the level of the intermediate RNA transcripts. The magnitude of the decrease closely parallels that observed when transposed copies are assayed by selection of G418-resistant cells. Moreover, sequencing of transposed elements recovered by PCR without prior selection of the cells reveals high-level editing. Using this direct method with a series of cytosine deaminases, we further demonstrate a similar dual effect of African green monkey APOBE3G, human APOBEC3F and murine APOBEC3 on MusD retrotransposition, with a distinct extent and site specificity for each editing activity. Altogether the data demonstrate that cytosine deaminases have a protective effect against endogenous retroviruses both by reducing viral cDNA levels and by introducing mutations in the transposed copies, thus inactivating them for subsequent rounds of retrotransposition. This dual, two-step effect likely participates in the efficient defense of the cell genome against invading endogenous retroelements

Restriction by APOBEC3 proteins of endogenous retroviruses with an extracellular life cycle: ex vivo effects and in vivo "traces" on the murine IAPE and human HERV-K elements

<p>Abstract</p> <p>Background</p> <p>APOBEC3 cytosine deaminases have been demonstrated to restrict infectivity of a series of retroviruses, with different efficiencies depending on the retrovirus. In addition, APOBEC3 proteins can severely restrict the intracellular transposition of a series of retroelements with a strictly intracellular life cycle, including the murine IAP and MusD LTR-retrotransposons.</p> <p>Results</p> <p>Here we show that the IAPE element, which is the infectious progenitor of the strictly intracellular IAP elements, and the infectious human endogenous retrovirus HERV-K are restricted by both murine and human APOBEC3 proteins in an <it>ex vivo </it>assay for infectivity, with evidence in most cases of strand-specific G-to-A editing of the proviruses, with the expected signatures. <it>In silico </it>analysis of the naturally occurring genomic copies of the corresponding endogenous elements performed on the mouse and human genomes discloses "traces" of APOBEC3-editing, with the specific signature of the murine APOBEC3 and human APOBEC3G enzymes, respectively, and to a variable extent depending on the family member.</p> <p>Conclusion</p> <p>These results indicate that the IAPE and HERV-K elements, which can only replicate via an extracellular infection cycle, have been restricted at the time of their entry, amplification and integration into their target host genomes by definite APOBEC3 proteins, most probably acting in evolution to limit the mutagenic effect of these endogenized extracellular parasites.</p

Modelado en 3D de una puerta de la ciudad de Rennes del siglo XV: Portes Mordelaises

[EN] The Portes Mordelaises, remnants of the medieval city walls of Rennes, France, has been the subject of several archaeological excavations until 2017. From these excavations, we created a three-dimensional (3D) model of the site reconstructed as it would have appeared during the 15th century, including the surrounding plus the interiors of its famed towers. Once our efforts and results were officially recognised as being of national interest by the French Ministry of Culture and Communication, Department of Heritage and the National Museum Service of France, we presented our virtual model reconstruction in an exhibition curated by the Museum of Bretagne, entitled "Rennes, les vies d'une ville" (Rennes, the Lives of a City). This approach to 3D reconstruction of the site served to further study Rennes’ origins, its construction, organisation, as well as its historic relationship to surrounding territories. The main objective of this work was to investigate, using of a significant and com[ES] Las Portes Mordelaises, restos de las murallas medievales de la ciudad de Rennes, Francia, han sido objeto de varias excavaciones arqueológicas hasta el año 2017. A partir de estas excavaciones, pudimos crear un modelo tridimensional (3D) del sitio reconstruido tal y como habría aparecido durante el siglo XV, incluyendo los terrenos circundantes así como los interiores de sus famosas torres. Una vez que nuestros esfuerzos y resultados fueron reconocidos oficialmente como de interés nacional por el Ministerio de Cultura y Comunicación de Francia, el Departamento de Patrimonio así como el Servicio Nacional de Museos de Francia, presentamos nuestra reconstrucción del modelo virtual en una exposición gestionada por el Museo de Bretaña titulada "Rennes, las vidas de una ciudad”. Este enfoque de la reconstrucción en 3D del sitio sirvió para profundizar en el estudio de los orígenes de Rennes, su construcción, su organización, así como su relación histórica con los territorios circundantes. EBarreau, J.; Esnault, E.; Foucher, J.; Six, M.; Le Faou, C. (2020). 3D modelling of a 15th century city gate of Rennes: Portes Mordelaises. Virtual Archaeology Review. 11(22):41-55. https://doi.org/10.4995/var.2020.12653OJS41551122Ahmad, T., Afzal, M., Hayat, F., Asif, H. S., Ahsan, S., & Saleem, Y. (2012). Need for software design methodology for remote sensing applications. Life Sci Journal, 9(3), 2152-2156.Al-Baghdadi, M. A. S. (2017). 3D printing and 3D scanning of our ancient history: Preservation and protection of our cultural heritage and identity. International Journal of Energy and Environment, 8(5), 441-456.Alix, C., Carron, D., Roux-Capron, E., & Josserand, L. (2016). La porte Bannier, entrée principale de la ville d'Orléans aux XIVe-XVe siècles. Archeologie medievale, (46), 91-122. https://doi.org/10.4000/archeomed.2781Athanasoulis, D., Georgiou, A., Simou, X., Sfika, A., Klotsa, V., Zirogianni, T., Theodoropoulos, C., & Deligianni, E.-O. (2015). Bridging monuments through digital repository and graphic reconstruction methodologies. The Digital Enhancement Project of Argolid, Arcadia and Corinthia castles, Greece. In 2015 Digital Heritage, Vol. 1, (pp. 107- 110). Granada, Spain. https://doi.org/10.1109/digitalheritage.2015.7413846Auer, C. (2017). L'archéologie high tech - xenius arte. Retrieved February 16, 2017, from www.cnrs.fr/CNRSHebdo/bretagne-paysdeloire/actus.php?numero=11666Banfi, F., Brumana, R., & Stanga, C. (2019). Extended reality and informative models for the architectural heritage: from scan-to-BIM process to virtual and augmented reality. Virtual Archaeology Review, 10(21), 14-30. https://doi.org/10.4995/var.2019.11923Barreau, J. B. (2017). Techniques de production, d'exploration et d'analyse d'environnements archéologiques virtuels.(Production, exploration and analysis techniques of virtual archaeological environments) (Doctoral dissertation, INSA de Rennes, France). Retrieved from https://tel.archives-ouvertes.fr/tel-01633811/documentBarreau, J.-B., Bernard, Y., Petit, Q., Beuchet, L., Petit, E., Platen, V., Gaugne, R., Le Rumeur, J., & Gouranton, V. (2014). Combination of 3D scanning, modeling and analyzing methods around the castle of Coatfrec reconstitution. In Digital Heritage. Progress in Cultural Heritage: Documentation, Preservation, and Protection. EuroMed 2014 (pp. 418-426). Limassol, Cyprus. https://doi.org/10.1007/978-3-319-13695-0_40Barreau, J.-B., Gaugne, R., Bernard, Y., Le Cloirec, G., & Gouranton, V. (2013). The West Digital Conservatory of Archaelogical Heritage project. In 2013 Digital Heritage (pp. 1-8). Marseille, France. https://doi.org/10.1109/digitalheritage.2013.6743795Barreau, J.-B., Lanoe, E., & Gaugne, R. (2020). 3D sketching of the fortified entrance of the citadel of Aleppo from a few sightseeing photos. In Kremers H. (Ed.), Digital Cultural Heritage (pp. 359-371). Cham: Springer International Publishing. https://doi.org/10.1007/978-3-030-15200-0_24Barrera-Vera, J. A. (2005). Generation of virtual models of historical tapial walls in Seville (Spain). In VSMM 2005: proceedings of the eleventh International Conference on Virtual Systems and Multimedia: Virtual reality at work in the 21st century: impact on society. Ghent, Belgium.Bayraktar, C. (2016). V-RAY 3.3. Istanbul: Kodlab Yayin Dağitim Yazilim Ltd.şti.Boochs, F., Hoffmann, A., Huxhagen, U., & Welter, D. (2006). Digital reconstruction of archeological objects using hybrid sensing techniques-The example Porta Nigra at Trier. Bar International Series, 1568, 395-400.Bosser, A. G. (2004). Massively multi-player games: Matching game design with technical design. In Proceedings of the 2004 ACM SIGCHI International Conference on Advances in computer entertainment technology (pp. 263-268). Singapore. https://doi.org/10.1145/1067343.1067378Brioso, X., Calderón, C., Aguilar, R., & Pando, M. A. (2019). Preliminary methodology for the integration of lean construction, bim and virtual reality in the planning phase of structural intervention in heritage structures. In Structural Analysis of Historical Constructions (pp. 484-492). Cusco, Peru. https://doi.org/10.1007/978-3-319-99441-3_52Canciani, M., Conigliaro, E., Grasso, M. D., Papalini, P., & Saccone, M. (2016). 3D survey and augmented reality for cultural heritage. The case study of Aurelian wall at Castra Praetoria in Rome. International Archives of the Photogrammetry, Remote Sensing & Spatial Information Sciences, XLI-B5, 931-937. https://doi.org/10.5194/isprsarchives-xli-b5-931-2016Carrión-Ruiz, B., Blanco-Pons, S., Weigert, A., Fai, S., & Lerma, J. L. (2019). Merging photogrammetry and augmented reality: The Canadian Library of Parliament. International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, 42(2/W11), 367-371. https://doi.org/10.5194/isprs-archives-xlii-2-w11-367-2019Châtellier, L. (2011). Modélisation 3d: la porte Cailhau. Retrieved May 20, 2011, from https://www.kiwimage.com/2011/3d/modelisation-3d-la-porte-cailhau/Contenson, L. D. (1907). Les remparts de Rennes. Bulletin Monumental, 71(1), 431-441. https://doi.org/10.3406/bulmo.1907.11425Debacker, P. (2019). Grâce aux nouvelles technologies, les archeologues sont plus efficaces. Retrieved June 14, 2019, from https://www.1jour1actu.com/science/grace-aux-nouvelles-technologies-les-archeologues-sont-plus-efficacesDelone, W. H., & McLean, E. R. (2003). The DeLone and McLean model of Information Systems success: a ten-year update. Journal of Management Information Systems, 19(4), 9-30. https://doi.org/10.1080/07421222.2003.11045748Du Crest de Villeneuve, E.-R., & Lorette, H. (1841). Album Breton: souvenirs de Rennes. Rennes: Ambroise Jausions.Esnault, E. (2012). RENNES (35). Les Portes Mordelaises. Rapport intermédiaire de fp. Fouille programmée, RAP02792, Service Régional de l'Archéologie de Bretagne. Retrieved from http://bibliotheque.numerique.srabretagne.fr/files/original/d5dcfe1a4491a228ffac3aa84cca0226.pdfEsnault, E. (2013). Rennes (Ille-et-Vilaine). Les portes Mordelaises. Archéologie Médiévale, 43, 273-274.Esnault, E. (2014a). RENNES (35). Les Portes Mordelaises. Rapport intermédiaire de fp 2012-2014. Fouille programmée, RAP02919, Service Régional de l'Archéologie de Bretagne. Retrieved from http://bibliotheque.numerique.sra-bretagne.fr/files/original/f3e868678cdd1dd64a9cd2fd12efde4b.pdfEsnault, E. (2014b). Rennes (Ille-et-Vilaine). Les portes Mordelaises. Archéologie Médiévale, 44, 279.Esnault, E. (2015a). RENNES (35). Les Portes Mordelaises. Rapport intermédiaire de fp. Fouille programmée, RAP03063, Service Régional de l'Archéologie de Bretagne. Retrieved from http://bibliotheque.numerique.srabretagne.fr/files/original/912019e9c7133236f6611868b3b0fa86.pdfEsnault, E. (2015b). Rennes (Ille-et-Vilaine). Les portes Mordelaises. Archéologie Médiévale, 45, 250-251.Esnault, E. (2016a). RENNES (35). Les Portes Mordelaises. Rapport intermediaire 2015 de FP. Fouille programmée, RAP03203, Service Régional de l'Archéologie de Bretagne. Retrieved from http://bibliotheque.numerique.srabretagne.fr/files/original/034c4915717c242d2af1df753ce91089.pdfEsnault, E. (2016b). Rennes (Ille-et-Vilaine). Les portes Mordelaises. Archéologie Médiévale, 46, 266-267.Esnault, E. (2017a). RENNES (35). Les Portes Mordelaises. Rapport intermediaire 2016 de FP. Fouille programmée, RAP03386, Service Régional de l'Archéologie de Bretagne. Retrieved from http://bibliotheque.numerique.srabretagne.fr/files/original/bcc431b25e3267e4b6995701b6af4594.pdfEsnault, E. (2017b). Rennes (Ille-et-Vilaine). Les portes Mordelaises. Archéologie Médiévale, 47, 246-247.Esnault, E. (2018a). Les fortifications médiévales et les Portes Mordelaises. Retrieved January 5, 2020 from https://multimedia.inrap.fr/atlas/Rennes/syntheses/par-themes/Les-fortifications-medievales-et-les-PortesMordelaises#.XhzRNiNCeUkEsnault, E. (2018b). Les nouvelles techniques de relevés appliquées à l'archéologie du bâti et à l'archéologie urbaine. In S. Eusèbe, T. Nicolas, V. Gouranton, & R. Gaugne (Dir.) - Archéologie: imagerie numérique et 3D: Actes du 3e Séminaire Scientifique et Technique de l'Inrap, 26-27 juin 2018. Rennes, France. Retrieved from https://sstinrap.hypotheses.org/501Esnault, E. (2018c). RENNES (35). Les Portes Mordelaises. Rapport intermediaire 2017 de FP. Fouille programmée, RAP03512, Service Régional de l'Archéologie de Bretagne. Retrieved from http://bibliotheque.numerique.srabretagne.fr/files/original/d517bc059b5dd79cc80d0997777a3f0b.pdfFerko, A., Martinka, J., Sormann, M., Karner, K., Zara, J., & Krivograd, S. (2004). Virtual Heart of Central Europe. In Proceedings of 9th symposion on Info & Communication Technology in Urban and Spatial planning and Impacts of ICT on Physical Space (pp. 193-200). Wien, Austria.Fisher, M., & Hanrahan, P. (2010). Context-based search for 3D models. ACM transactions on Graphics (TOG), 29(6), 182. https://doi.org/10.1145/1882261.1866204Freudenberg, B., Masuch, M., Rober, N., & Strothotte, T. (2001). The Computer-Visualistik-Raum: veritable and inexpensive presentation of a virtual reconstruction. In Proceedings of the 2001 conference on Virtual Reality, Archeology, and Cultural Heritage (pp. 97-102) Glyfada, Greece. https://doi.org/10.1145/585009.585010Gaugne, R., Gouranton, V., Dumont, G., Chauffaut, A., & Arnaldi, B. (2014). Immersia, an open immersive infrastructure: doing archaeology in virtual reality. Archeologia e Calcolatori, suppl. 5, 1-10.Guillas, N. (2013). Des drones qui fouillent le sol. Sciences Ouest, 312.Haller, M. (2004). Photorealism or/and non-photorealism in augmented reality. In Proceedings of the 2004 ACM SIGGRAPH International Conference on Virtual Reality Continuum and its Applications in Industry (pp. 189-196). Singapore. https://doi.org/10.1145/1044588.1044627Hoda, R., Salleh, N., & Grundy, J. (2018). The rise and evolution of agile software development. IEEE Software, 35(5), 58-63. https://doi.org/10.1109/ms.2018.290111318Inrap (2018). Archéologie de la ville de Rennes, carte des sites de fouilles. Retrieved January 3, 2020, from https://multimedia.inrap.fr/atlas/Rennes/archeo-RennesInrap (2019). Rennes. Retrieved January 8, 2020, from https://www.inrap.fr/communes/rennesJahn, I., Kersten, T., & Kinzel, R. (2004). Erfahrungen mit einem 3d-laserscanning-system bei der erfassung einer industrieanlage und des lubecker holstentores. Photogrammetrie-Laserscanning-Optische 3D-Messtechnik (pp. 222- 229).Koutonen, J., & Leppänen, M. (2013). How are agile methods and practices deployed in video game development? A survey into Finnish game studios. In International Conference on Agile Software Development (pp. 135-149). Berlin, Germany. https://doi.org/10.1007/978-3-642-38314-4_10Le Cloirec, G. (2019). Du crayon au SIG: 30 ans d'archeologie urbaine à Rennes. Retrieved August 5, 2019, from https://musee-devoile.blog/2019/08/05/du-crayon-au-sig-30-ans-darcheologie-urbaine-a-rennesLópez, L., Arroyo, G., & Martín, D. (2012). Computer tool for automatically generated 3D illustration in real time from archeological scanned pieces. Virtual Archaeology Review, 3(6), 73-77. https://doi.org/10.4995/var.2012.4447Marek, M., & Hipp, K. (2011). Cracovia 3D: rekonstrukcje cyfrowe historycznej zabudowy Krakowa. Kraków: Kolegium Wydawnicze Muzeum Historycznego Miasta Krakowa.Ouest-France (2013). L'histoire des Portes mordelaises se visite. Retrieved April 25, 2013 from https://www.ouestfrance.fr/bretagne/rennes-35000/lhistoire-des-portes-mordelaises-se-visite-1078116Mora, P., & Vivier, A. (2007). Le levé tachéométrique et son utilisation dans la numérisation de sites archéologiques. In Virtual Retrospect, 3 (pp. 203-206). Pessac, France.Mortara, M., & Catalano, C. (2018). 3D Virtual environments as effective learning contexts for cultural heritage. Italian Journal of Educational Technology, 26(2), 5-21. https://doi.org/10.17471/2499-4324/1026Ouest-France (2019). "Rennes, les vies d'une ville", une exposition qui vous fait voyager dans le temps. Retrieved January 26, 2019 from https://www.ouest-france.fr/bretagne/rennes-35000/rennes-les-vies-d-une-ville-uneexposition-qui-vous-fait-voyager-dans-le-temps-6197410Ozimek, P. (2007). Rekonstrukcja wirtualna obiektow architektonicznych. Roczniki Geomatyki-Annals of Geomatics, 5(8), 173-185.Pybus, C., Graham, K., Doherty, J., Arellano, N., & Fai, S. (2019). New realities for Canada's Parliament: a workflow for preparing heritage bim for game engines and virtual reality. International Archives of the Photogrammetry, Remote Sensing & Spatial Information Sciences, XLII-2/W15, 945-952. https://doi.org/10.5194/isprs-archives-XLII-2-W15945-2019Regnard, A.-L. (2015). Construction de la maquette 3D de Rennes Métropole: mise en place, analyse et optimisation des processus (Master's thesis, CNAM - École Supérieure des Géomètres et Topographes, Le Mans, France).Remondino, F. (2003). From point cloud to surface: the modeling and visualization problem. International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences, XXXIV-5/W10.Resco, P. A., & Figueidero, C. (2014). Escala de evidencia histórica | Scale of historical evidence. Retrieved January 10, 2015, from https://parpatrimonioytecnologia.wordpress.com/2014/07/21/escala-de-evidencia-historica-scale-ofhistorical-evidenceSix, M. (2018). Rennes, les vies d'une ville. Rennes: Presses Universitaires de Rennes.Tucci, G., Conti, A., Fiorini, L., Corongiu, M., Valdambrini, N., & Matta, C. (2019). M-BIM: a new tool for the Galleria dell'Accademia di Firenze. Virtual Archaeology Review, 10(21), 40-55. https://doi.org/10.4995/var.2019.11943Veillard, K. (2015). Plongeon dans le passé ce week-end avec les journées de l'Archéologie. Retrieved June 18, 2015, from https://france3-regions.francetvinfo.fr/bretagne/2015/06/18/plongeon-dans-le-passe-ce-week-end-avec-lesjournees-de-l-archeologie-749959.htmlZhangyu, D. (2014). Capital gatekeeper. Retrieved November 19, 2014, from http://www.chinadaily.com.cn/beijing/201411/19/content_18939388.ht

Sterol composition of three marine sponge species from the genus Cinachyrella

The hitherto undescribed sterol composition of three marine sponge species belonging to the genus #Cynachyrella are reported : #C. alloclada and #C. kukenthali from the Senegalese coast, at two different depths, and C. aff. #schultezei from the lagoon of Nouméa, New Caledonia. (D'après résumé d'auteur

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Arsenic: Une thérapie de choix dans la leucémie aiguë promyélocytaire avec mutation FLT3-ITD

International audienc

The GLN Family of Murine Endogenous Retroviruses Contains an Element Competent for Infectious Viral Particle Formation▿

Several families of endogenous retroviruses (ERVs) have been identified in the mouse genome, in several instances by in silico searches, but for many of them it remains to be determined whether there are elements that can still encode functional retroviral particles. Here, we identify, within the GLN family of highly reiterated ERVs, one, and only one, copy that encodes retroviral particles prone to infection of mouse cells. We show that its envelope protein confers an ecotropic host range and recognizes a receptor different from mCAT1 and mSMIT1, the two previously identified receptors for other ecotropic mouse retroviruses. Electron microscopy disclosed viral particle assembly and budding at the cell membrane, as well as release of mature particles into the extracellular space. These particles are closely related to murine leukemia virus (MLV) particles, with which they have most probably been confused in the past. This study, therefore, identifies a new class of infectious mouse ERVs belonging to the family Gammaretroviridae, with one family member still functional today. This family is in addition to the two MLV and mouse mammary tumor virus families of active mouse ERVs with an extracellular life cycle