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Medline ® Abstracts for References 6-10

of 'Zika virus infection: An overview'

6
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Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth.
AU
Tang H, Hammack C, Ogden SC, Wen Z, Qian X, Li Y, Yao B, Shin J, Zhang F, Lee EM, Christian KM, Didier RA, Jin P, Song H, Ming GL
SO
Cell Stem Cell. 2016;18(5):587. Epub 2016 Mar 4.
 
The suspected link between infection by Zika virus (ZIKV), a re-emerging flavivirus, and microcephaly is an urgent global health concern. The direct target cells of ZIKV in the developing human fetus are not clear. Here we show that a strain of the ZIKV, MR766, serially passaged in monkey and mosquito cells efficiently infects human neural progenitor cells (hNPCs) derived from induced pluripotent stem cells. Infected hNPCs further release infectious ZIKV particles. Importantly, ZIKV infection increases cell death and dysregulates cell-cycle progression, resulting in attenuated hNPC growth. Global gene expression analysis of infected hNPCs reveals transcriptional dysregulation, notably of cell-cycle-related pathways. Our results identify hNPCs as a direct ZIKV target. In addition, we establish a tractable experimental model system to investigate the impact and mechanism of ZIKV on human brain development and provide a platform to screen therapeutic compounds.
AD
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA. Electronic address: tang@bio.fsu.edu.
PMID
7
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Zika Virus Associated with Microcephaly.
AU
Mlakar J, Korva M, Tul N, PopovićM, Poljšak-Prijatelj M, Mraz J, Kolenc M, Resman Rus K, Vesnaver Vipotnik T, Fabjan Vodušek V, Vizjak A, Pižem J, Petrovec M, AvšičŽupanc T
SO
N Engl J Med. 2016;374(10):951. Epub 2016 Feb 10.
 
A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain.
AD
From the Institute of Pathology, Faculty of Medicine (J. Mlakar, M. Popović, J. Mraz, A.V., J.P.), and the Institute of Microbiology and Immunology, Faculty of Medicine (M. Korva, M.P.-P., M. Kolenc, K.R.R., M. Petrovec, T.A.Z.), University of Ljubljana, and the Department of Perinatology, Division of Gynecology and Obstetrics (N.T., V.F.V.), and the Institute of Radiology (T.V.V.), University Medical Center Ljubljana - all in Ljubljana, Slovenia.
PMID
8
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Expression Analysis Highlights AXL as a Candidate Zika Virus Entry Receptor in Neural Stem Cells.
AU
Nowakowski TJ, Pollen AA, Di Lullo E, Sandoval-Espinosa C, Bershteyn M, Kriegstein AR
SO
Cell Stem Cell. 2016;18(5):591. Epub 2016 Mar 30.
 
The recent outbreak of Zika virus (ZIKV) in Brazil has been linked to substantial increases in fetal abnormalities and microcephaly. However, information about the underlying molecular and cellular mechanisms connecting viral infection to these defects remains limited. In this study we have examined the expression of receptors implicated in cell entry of several enveloped viruses including ZIKV across diverse cell types in the developing brain. Using single-cell RNA-seq and immunohistochemistry, we found that the candidate viral entry receptor AXL is highly expressed by human radial glial cells, astrocytes, endothelial cells, and microglia in developing human cortex and by progenitor cells in developing retina. We also show that AXL expression in radial glia is conserved in developing mouse and ferret cortex and in human stem cell-derived cerebral organoids, highlighting multiple experimental systems that could be applied to study mechanisms of ZIKV infectivity and effects on brain development.
AD
Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
PMID
9
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The 3.8Åresolution cryo-EM structure of Zika virus.
AU
Sirohi D, Chen Z, Sun L, Klose T, Pierson TC, Rossmann MG, Kuhn RJ
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Science. 2016;352(6284):467. Epub 2016 Mar 31.
 
The recent rapid spread of Zika virus and its unexpected linkage to birth defects and an autoimmune neurological syndrome have generated worldwide concern. Zika virus is a flavivirus like the dengue, yellow fever, and West Nile viruses. We present the 3.8 angstrom resolution structure of mature Zika virus, determined by cryo-electron microscopy (cryo-EM). The structure of Zika virus is similar to other known flavivirus structures, except for the ~10 amino acids that surround the Asn(154) glycosylation site in each of the 180 envelope glycoproteins that make up the icosahedral shell. The carbohydrate moiety associated with this residue, which is recognizable in the cryo-EM electron density, may function as an attachment site of the virus to host cells. This region varies not only among Zika virus strains but also in other flaviviruses, which suggests that differences in this region may influence virus transmission and disease.
AD
Markey Center for Structural Biology and Purdue Institute for Inflammation, Immunology and Infectious Disease, Purdue University, West Lafayette, IN 47907, USA.
PMID
10
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Zika virus impairs growth in human neurospheres and brain organoids.
AU
Garcez PP, Loiola EC, Madeiro da Costa R, Higa LM, Trindade P, Delvecchio R, Nascimento JM, Brindeiro R, Tanuri A, Rehen SK
SO
Science. 2016;352(6287):816.
 
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.
AD
Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil. D'Or Institute for Research and Education (IDOR), Rio de Janeiro, Brazil.
PMID