Consellho Nacional de Desenvolvimento e Pesquisa (CNPq), Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ).
Since the emergence of Zika virus (ZIKV), reports of microcephaly have increased considerably in Brazil; however, causality between the viral epidemic and malformations in fetal brains needs further confirmation. We examined the effects of ZIKV infection in human neural stem cells growing as neurospheres and brain organoids. Using immunocytochemistry and electron microscopy, we showed that ZIKV targets human brain cells, reducing their viability and growth as neurospheres and brain organoids. These results suggest that ZIKV abrogates neurogenesis during human brain development. P rimary microcephaly is a severe brain malformation characterized by the reduction of the head circumference. Patients display a heterogeneous range of brain impairments that compromise motor, visual, hearing, and cognitive functions (1).Microcephaly is associated with decreased neuronal production as a consequence of proliferative defects and death of cortical progenitor cells (2). During pregnancy, the primary etiology of microcephaly varies from genetic mutations to external insults. The so-called TORCHS factors (toxoplasmosis, rubella, cytomegalovirus, herpes virus, and syphilis) are the main congenital infections that compromise brain development in utero (3).An increase in the rate of microcephaly in Brazil has been associated with the recent outbreak of Zika virus (ZIKV) (4, 5), a flavivirus that is transmitted by mosquitoes (6) and sexually (7-9). So far, ZIKV has been described in the placenta and amniotic fluid of microcephalic fetuses (10-13) and in the blood of microcephalic newborns (11, 14). ZIKV had also been detected within the brain of a microcephalic fetus (13, 14), and recently, direct evidence has emerged that ZIKV is able to infect and cause the death of neural stem cells (15).We used human induced pluripotent stem (iPS) cells cultured as neural stem cells (NSCs), neurospheres, and brain organoids to explore the consequences of ZIKV infection during neurogenesis and growth with three-dimensional culture models. Human iPS-derived NSCs were exposed to ZIKV [multiplicity of infection (MOI), 0.25 to 0.0025]. After 24 hours, ZIKV was detected in NSCs (Fig. 1, A to D); viral envelope protein was evident in 10.10% (MOI, 0.025) and 21.7% (MOI, 0.25) of cells exposed to ZIKV (Fig. 1E). Viral RNA was also detected in the supernatant of infected NSCs (MOI, 0.0025) by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) ( Fig. 1F), providing evidence of productive infection.To investigate the effects of ZIKV during neural differentiation, mock-and ZIKV-infected NSCs were cultured as neurospheres. After 3 days in vitro (DIV), mock-infected NSCs generated round neurospheres. However, ZIKVinfected NSCs generated neurospheres with morphological abnormalities and cell detachment ( Mock-infected neurospheres presented the expected ultrastructural morphology of the nucleus and mitochondria (Fig. 3A). Viral particles were present in ZIKV-infected neurospheres, similar to those observed in murine glial and neuronal cel...
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.
The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.
Purpose To document the imaging findings associated with congenital Zika virus infection as found in the Instituto de Pesquisa in Campina Grande State Paraiba (IPESQ) in northeastern Brazil, where the congenital infection has been particularly severe. Materials and Methods From June 2015 to May 2016, 438 patients were referred to the IPESQ for rash occurring during pregnancy or for suspected fetal central nervous system abnormality. Patients who underwent imaging at IPESQ were included, as well as those with documented Zika virus infection in fluid or tissue (n = 17, confirmed infection cohort) or those with brain findings suspicious for Zika virus infection, with intracranial calcifications (n = 28, presumed infection cohort). Imaging examinations included 12 fetal magnetic resonance (MR) examinations, 42 postnatal brain computed tomographic examinations, and 11 postnatal brain MR examinations. Images were reviewed by four radiologists, with final opinion achieved by means of consensus. Results Brain abnormalities seen in confirmed (n = 17) and presumed (n = 28) congenital Zika virus infections were similar, with ventriculomegaly in 16 of 17 (94%) and 27 of 28 (96%) infections, respectively; abnormalities of the corpus callosum in 16 of 17 (94%) and 22 of 28 (78%) infections, respectively; and cortical migrational abnormalities in 16 of 17 (94%) and 28 of 28 (100%) infections, respectively. Although most fetuses underwent at least one examination that showed head circumference below the 5th percentile, head circumference could be normal in the presence of severe ventriculomegaly (seen in three fetuses). Intracranial calcifications were most commonly seen at the gray matter-white matter junction, in 15 of 17 (88%) and 28 of 28 (100%) confirmed and presumed infections, respectively. The basal ganglia and/or thalamus were also commonly involved with calcifications in 11 of 17 (65%) and 18 of 28 (64%) infections, respectively. The skull frequently had a collapsed appearance with overlapping sutures and redundant skin folds and, occasionally, intracranial herniation of orbital fat and clot in the confluence of sinuses. Conclusion The spectrum of findings associated with congenital Zika virus infection in the IPESQ in northeastern Brazil is illustrated to aid the radiologist in identifying Zika virus infection at imaging. (©) RSNA, 2016 Online supplemental material is available for this article.
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