1. The Brazilian Zika virus strain causes birth defects in experimental models
- Author
-
David G. Andrade, Amadou A. Sall, Graciela Conceição Pignatari, Erica A. Mendes, Carlos Alberto Buchpigel, Katia de Oliveira Pimenta Guimarães, Carla Torres Braconi, Isabella Rodrigues Fernandes, Cristiano Rossato, Daniele de Paula Faria, João Leonardo Rodrigues Mendonça Dias, Fabiele Baldino Russo, Fernanda R. Cugola, Beatriz C.G. Freitas, Patricia Cristina Baleeiro Beltrão-Braga, Alysson R. Muotri, Alexandre T. Garcez, Nathalia Almeida, Jean Pierre Schatzmann Peron, Carolina Manganeli Polonio, Cecilia Benazzato, Paolo Marinho de Andrade Zanotto, Carla Longo de Freitas, Sarah Romero, Wesley Nogueira Brandão, and Isabela Werneck da Cunha
- Subjects
0301 basic medicine ,Microcephaly ,Placenta ,Prevalence ,Apoptosis ,Low Birth Weight and Health of the Newborn ,Zika virus ,Mice ,0302 clinical medicine ,Neural Stem Cells ,Pregnancy ,Infant Mortality ,2.2 Factors relating to the physical environment ,2.1 Biological and endogenous factors ,Aetiology ,Pediatric ,Multidisciplinary ,Fetal Growth Retardation ,Zika Virus Infection ,Brain ,3. Good health ,Organoids ,Infectious Diseases ,Female ,Infection ,Brazil ,General Science & Technology ,Intellectual and Developmental Disabilities (IDD) ,Biology ,Arbovirus ,Virus ,03 medical and health sciences ,Fetus ,Rare Diseases ,Preterm ,medicine ,Autophagy ,Animals ,Progenitor cell ,MICROCEFALIA ,Cell Proliferation ,Animal ,Neurosciences ,Outbreak ,Zika Virus ,Perinatal Period - Conditions Originating in Perinatal Period ,biology.organism_classification ,medicine.disease ,Virology ,Brain Disorders ,Disease Models, Animal ,030104 developmental biology ,Front Matter: Discovery ,Immunology ,Disease Models ,Congenital Structural Anomalies ,030217 neurology & neurosurgery - 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.
- Published
- 2016