Zika Virus Strains and Dengue Virus Induce Distinct Proteomic Changes in Neural Stem Cells and Neurospheres

Nascimento, Juliana; Gouvêa-Junqueira, Danielle; Zuccoli, Giuliana S.; Pedrosa, Carolina da S. G.; Brandão‐Teles, Caroline; Crunfli, Fernanda; Antunes, André Saraiva Leão Marcelo; Cassoli, Juliana S.; Karmirian, Karina; Salerno, José Alexandre; Souza, Gabriela Fabiano de; Muraro, Stéfanie Primon; Proença-Módena, José Luiz; Higa, Luiza M.; Tanuri, Amílcar; Garcez, Patrícia P.; Rehen, Stevens K.; Martins-de-Souza, Daniel

doi:10.1007/s12035-022-02922-3

Cited by 4 publications

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“…Although the epidemiology of Zika congenital syndrome corresponds to infections with strains of the Asian lineage ( Simonin et al, 2017 ; Aubry et al, 2021 ; Hamel et al, 2017 ), phenotypic changes in the viral proteins that may have produced these pathogenic variants mainly correlate with protein mutations in sites involved in the host immune recognition ( Hamel et al, 2017 ; Jung et al, 2022 ; Sironi et al, 2016 ). Therefore, these alterations are likely to enhance a greater efficiency of the virus to cross the placental and fetal blood brain barrier yet unlikely to cause differences in the infectivity in 2D and 3D in vitro systems ( Hamel et al, 2017 ; Xu et al, 2019 ; Muffat et al, 2018 ; Garcez et al, 2016 , 2017 ; Nascimento et al, 2022 ). To confirm this, we performed a single round of infection in hi-NPCs using a highly pathogenic Asian strain (PRVABC59) and a less pathogenic African strain U-1962 (MP1751) obtaining similar infectivity results ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Zika virus-induces metabolic alterations in fetal neuronal progenitors that could influence in neurodevelopment during early pregnancy

et al. 2023

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Cortical development consists of an orchestrated process in which progenitor cells exhibit distinct fate restrictions regulated by time-dependent activation of energetic pathways. Thus, the hijacking of cellular metabolism by Zika virus (ZIKV) to support its replication may contribute to damage in the developing fetal brain. Here, we showed that ZIKV replicates differently in two glycolytically distinct pools of cortical progenitors derived from human induced pluripotent stem cells (hiPSCs), which resemble the metabolic patterns of quiescence (early hi-NPCs) and immature brain cells (late hi-NPCs) in the forebrain. This differential replication alters the transcription of metabolic genes in both pools of cortical progenitors but solely upregulates the glycolytic capacity of early hi-NPCs. Analysis using Imagestream® revealed that, during early stages of ZIKV replication, in early hi-NPCs there is an increase in lipid droplet abundance and size. This stage of ZIKV replication significantly reduced the mitochondrial distribution in both early and late hi-NPCs. During later stages of ZIKV replication, late hi-NPCs show reduced mitochondrial size and abundance. The finding that there are alterations of cellular metabolism during ZIKV infection which are specific to pools of cortical progenitors at different stages of maturation may help to explain the differences in brain damage over each trimester.

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