The cyanobacterial saxitoxin exacerbates neural cell death and brain malformations induced by zika virus

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water sup-plies of NE compared to other regions of Brazil. Experimentally, we described that STX dou-bled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.Fil: Pedrosa, Carolina da S. G.. D’Or Institute for Research and Education; BrasilFil: Souza, Leticia R. Q.. D’Or Institute for Research and Education; BrasilFil: Gomes, Tiago A.. Universidade Federal do Rio de Janeiro; Brasil. Instituto Oswaldo Cruz; BrasilFil: de Lima, Caroline V. F.. D’Or Institute for Research and Education; BrasilFil: Ledur, Pitia F.. D’Or Institute for Research and Education; BrasilFil: Karmirian, Karina. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Barbeito Andrés, Jimena. Universidade Federal do Rio de Janeiro; Brasil. Universidad Nacional Arturo Jauretche. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Provincia de Buenos Aires. Ministerio de Salud. Hospital Alta Complejidad en Red El Cruce Dr. Néstor Carlos Kirchner Samic. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Unidad Ejecutora de Estudios en Neurociencias y Sistemas Complejos; ArgentinaFil: Costa, Marcelo do N.. Universidade Federal do Rio de Janeiro; BrasilFil: Higa, Luiza M.. Universidade Federal do Rio de Janeiro; BrasilFil: Rossi, Átila D.. Universidade Federal do Rio de Janeiro; BrasilFil: Bellio, Maria. Universidade Federal do Rio de Janeiro; BrasilFil: Tanuri, Amilcar. Universidade Federal do Rio de Janeiro; BrasilFil: Prata Barbosa, Arnaldo. D’Or Institute for Research and Education; BrasilFil: Tovar Moll, Fernanda. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; BrasilFil: Garcez, Patricia P.. Universidade Federal do Rio de Janeiro; BrasilFil: Lara, Flavio A.. Instituto Oswaldo Cruz; BrasilFil: Molica, Renato J. R.. Universidad Federal Rural Pernambuco; BrasilFil: Rehen, Stevens K.. D’Or Institute for Research and Education; Brasil. Universidade Federal do Rio de Janeiro; Brasi

Use of the heteroduplex mobility assay and cell sorting to select genome sequences of the CCR5 gene in HEK 293T cells edited by transcription activator-like effector nucleases

Engineered nucleases such as zinc finger nucleases (ZFN) and transcription activator-like effector nucleases (TALEN) are one of the most promising tools for modifying genomes. These site-specific enzymes cause double- strand breaks that allow gene disruption or gene insertion, thereby facilitating genetic manipulation. The major problem associated with this approach is the labor-intensive procedures required to screen and confirm the cellular modification by nucleases. In this work, we produced a TALEN that targets the human CCR5 gene and developed a heteroduplex mobility assay for HEK 293T cells to select positive colonies for sequencing. This approach provides a useful tool for the quick detection and easy assessment of nuclease activity

Data from: Evolution and epidemic spread of SARS-CoV-2 in Brazil

Brazil currently has one of the fastest growing SARS-CoV-2 epidemics in the world. Owing to limited available data, assessments of the impact of non-pharmaceutical interventions (NPIs) on virus spread remain challenging. Using a mobility-driven transmission model, we show that NPIs reduced the reproduction number from >3 to 1–1.6 in São Paulo and Rio de Janeiro. Sequencing of 427 new genomes and analysis of a geographically representative genomic dataset identified >100 international virus introductions in Brazil. We estimate that most (76%) of the Brazilian strains fell in three clades that were introduced from Europe between 22 February11 March 2020. During the early epidemic phase, we found that SARS-CoV-2 spread mostly locally and within-state borders. After this period, despite sharp decreases in air travel, we estimated multiple exportations from large urban centers that coincided with a 25% increase in average travelled distances in national flights. This study sheds new light on the epidemic transmission and evolutionary trajectories of SARS-CoV-2 lineages in Brazil, and provide evidence that current interventions remain insufficient to keep virus transmission under control in the country