The Brazilian Zika virus strain causes birth defects in experimental models
Fernanda R. Cugola,Isabella Rodrigues Fernandes,Isabella Rodrigues Fernandes,Fabiele Baldino Russo,Beatriz C.G. Freitas,João Leonardo Rodrigues Mendonça Dias,Katia de Oliveira Pimenta Guimarães,Cecilia Benazzato,Nathalia Almeida,Graciela Conceição Pignatari,Sarah Romero,Carolina Manganeli Polonio,Isabela Werneck da Cunha,Carla Longo de Freitas,Wesley Nogueira Brandão,Cristiano Rossato,David G. Andrade,Daniele de Paula Faria,Alexandre T. Garcez,Carlos Alberto Buchpigel,Carla Torres Braconi,Erica A. Mendes,Amadou A. Sall,Paolo Marinho de Andrade Zanotto,Jean Pierre Schatzmann Peron,Alysson R. Muotri,Patricia Cristina Baleeiro Beltrão-Braga +26 more
TLDR
It is demonstrated that the ZIKVBR infects fetuses, causing intra-uterine growth restriction (IUGR), and crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, impairing neurodevelopment.Abstract:
Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barre syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.read more
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In situ immune response and mechanisms of cell damage in central nervous system of fatal cases microcephaly by Zika virus
Raimunda do Socorro da Silva Azevedo,Jorge Rodrigues de Sousa,Marialva Tereza Ferreira de Araújo,Arnaldo Jorge Martins Filho,Bianca Nascimento de Alcantara,Fernanda Montenegro de Carvalho Araújo,Maria G. L. Queiroz,Ana Cecília Ribeiro Cruz,Beatriz H. Baldez Vasconcelos,Jannifer Oliveira Chiang,Lívia Carício Martins,Livia Medeiros Neves Casseb,Eliana Vieira Pinto da Silva,Valéria Lima Carvalho,Barbara Cristina Baldez Vasconcelos,Sueli Rodrigues,Consuelo Silva de Oliveira,Juarez Antônio Simões Quaresma,Pedro Fernando da Costa Vasconcelos +18 more
TL;DR: The in situ immune response profile and mechanisms of neuronal cell damage in fatal Zika microcephaly cases were investigated and changes found were mainly calcification, necrosis, neuronophagy, gliosis, microglial nodules, and inflammatory infiltration of mononuclear cells.
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Induced pluripotent stem cell technology: a decade of progress
TL;DR: The progress in applications of iPSC technology that are particularly relevant to drug discovery and regenerative medicine are discussed, and the remaining challenges and the emerging opportunities in the field are considered.
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Transgenic Aedes aegypti Mosquitoes Transfer Genes into a Natural Population
Benjamin R. Evans,Panayiota Kotsakiozi,André Luis Costa-da-Silva,Rafaella Sayuri Ioshino,Luiza Garziera,Michele C. Pedrosa,Aldo Malavasi,Jair F. Virginio,Margareth Lara Capurro,Jefrey R. Powell +9 more
TL;DR: Evidently, rare viable hybrid offspring between the release strain and the Jacobina population are sufficiently robust to be able to reproduce in nature and highlight the importance of having in place a genetic monitoring program during releases to detect un-anticipated outcomes.
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Human organoids: model systems for human biology and medicine.
TL;DR: The applications, advantages and disadvantages of human organoids as models of development and disease and the challenges that have to be overcome for organoids to be able to substantially reduce the need for animal experiments are discussed.
Journal ArticleDOI
Cell diversity and network dynamics in photosensitive human brain organoids
Giorgia Quadrato,Giorgia Quadrato,Tuan V. Nguyen,Tuan V. Nguyen,Evan Z. Macosko,Evan Z. Macosko,John L. Sherwood,John L. Sherwood,Sung Min Yang,Daniel R. Berger,Natalie Maria,Jorg Scholvin,Melissa Goldman,Justin P. Kinney,Edward S. Boyden,Jeff W. Lichtman,Ziv Williams,Steven A. McCarroll,Steven A. McCarroll,Paola Arlotta,Paola Arlotta +20 more
TL;DR: It is found that organoids can generate a broad diversity of cells, which are related to endogenous classes, including cells from the cerebral cortex and the retina, which may offer a way to probe the functionality of human neuronal circuits using physiological sensory stimuli.
References
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Madeline A. Lancaster,Magdalena Renner,Carol Anne Martin,Daniel Wenzel,Louise S. Bicknell,Matthew E. Hurles,Tessa Homfray,Josef M. Penninger,Andrew P. Jackson,Juergen A. Knoblich +9 more
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Journal ArticleDOI
Zika Virus (I). Isolations and serological specificity
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Journal ArticleDOI
Genetic and Serologic Properties of Zika Virus Associated with an Epidemic, Yap State, Micronesia, 2007
Robert S. Lanciotti,Olga Kosoy,Janeen Laven,Jason O. Velez,Amy J. Lambert,Alison J. Johnson,Stephanie M. Stanfield,Mark R. Duffy +7 more
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Journal ArticleDOI
Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study
Van-Mai Cao-Lormeau,Alexandre Blake,Sandrine Mons,Stéphane Lastère,Claudine Roche,Jessica Vanhomwegen,Timothée Dub,Laure Baudouin,Anita Teissier,P. Larre,Anne-Laure Vial,Christophe Decam,Valérie Choumet,Susan K. Halstead,Hugh J. Willison,Lucile Musset,Jean-Claude Manuguerra,Philippe Desprès,Emmanuel Fournier,Henri-Pierre Mallet,Didier Musso,Arnaud Fontanet,Arnaud Fontanet,Jean Neil,Frédéric Ghawché +24 more
TL;DR: This is the first study providing evidence for Zika virus infection causing Guillain-Barré syndrome, and because Zika virus is spreading rapidly across the Americas, at risk countries need to prepare for adequate intensive care beds capacity to manage patients with Guillay-B Barré syndrome.
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