A cepa do vírus Zika causa defeitos de nascimento em modelos experimentais.
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 monkeys1. 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 Micronesia2. Patients experienced fever, skin rash, arthralgia and conjunctivitis2. 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 America3. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain–Barré syndrome4, 5. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKVBR) strain causes birth defects remains absent6. Here we demonstrate that ZIKVBR 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 ZIKVBR 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 ZIKVBR 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 ZIKVBR in human neurodevelopment.
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Authors: Fernanda R. Cugola, Isabella R. Fernandes, Fabiele B. Russo, Beatriz C. Freitas, João L. M. Dias, Katia P. Guimarães, Cecília Benazzato, Nathalia Almeida, Graciela C. Pignatari, Sarah Romero, Carolina M. Polonio, Isabela Cunha, Carla L. Freitas, Wesley N. Brandão, Cristiano Rossato, David G. Andrade, Daniele de P. Faria, Alexandre T. Garcez, Carlos A. Buchpigel, Carla T. Braconi, Erica Mendes, Amadou A. Sall, Paolo M. de A. Zanotto, Jean Pierre S. Peron, Alysson R. Muotri.
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