TY - JOUR T1 - The Impact of African and Brazilian ZIKV isolates on neuroprogenitors JF - bioRxiv DO - 10.1101/046599 SP - 046599 AU - Loraine Campanati AU - Luiza M. Higa AU - Rodrigo Delvecchio AU - Paula Pezzuto AU - Ana Luiza Valadão AU - Fábio L. Monteiro AU - Grasiella M. Ventura AU - Carla Veríssimo AU - Ana M. Bispo De Filippis AU - Renato S. Aguiar AU - Amilcar Tanuri Y1 - 2016/01/01 UR - http://biorxiv.org/content/early/2016/03/31/046599.abstract N2 - In the last few months, an overwhelming number of people have been exposed to the Zika virus (ZIKV) all over South and Central America. Healthcare professionals noticed an alarming surge of fetuses diagnosed with microcephaly and several other brain malformations from mothers who showed signs of the disease during pregnancy1-3. There was also an increase in the number of reported cases of Guillain-Barré syndrome that are now associated with the Zika epidemics4. Sequencing and phylogenetic data from our group showed that isolates from Brazilian patients are 97-100% identical to the virus isolated from the outbreak in the French Polynesia, while showing 87-90% identity to African isolates5. To date, there is no report of either cases of congenital abnormalities or Guillain-Barré syndrome in African countries, pointing to the possibility that differences in the genome sequences of these viral strains may be associated to different clinical outcomes. In this work we showed, in vitro, that the Brazilian virus has a greater impact on murine neuronal progenitors and neurons than the African strain MR766. We found that the Brazilian isolate more pronouncedly inhibits neurite extension from neurospheres, alters their differentiation potential and causes neurons to have less and shorter processes. Comparing both lineages using a panel of inflammatory cytokines, we showed, with human neuroblastoma cells, that ZIKV induces the production of several inflammatory and chemotactic cytokines and once again, the Brazilian isolate had a more significant impact in immune activation response. Although much more needs to be studied regarding the association of ZIKV infection and brain damage during development, our study sheds some light into the differences between African and American lineages and the mechanisms by which the virus may be affecting neurogenesis. ER -