Zika virus impairs growth in human neurospheres and brain organoids

Garcez, Patrícia P.; Loiola, Erick Correia; Costa, Rosa Maria Esteves Moreira da; Higa, Luiza M.; Trindade, Pablo; Delvecchio, Rodrigo; Nascimento, Juliana; Brindeiro, Rodrigo M.; Tanuri, Almicar; Rehen, Stevens

doi:10.7287/peerj.preprints.1817v1

Cited by 75 publications

(88 citation statements)

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“…The detection of ZIKV in fetal brains of humans (73)(74)(75)(76)(77) and mice (13,(78)(79)(80) has led to the hypothesis that virus replication in the CNS causes adverse perinatal outcomes. Although ZIKV is detectable in the fetal brain (20,81), we have shown that ZIKV is undetectable in the neonatal brain (13).…”

Section: Discussionmentioning

confidence: 99%

IL-1 receptor antagonist therapy mitigates placental dysfunction and perinatal injury following Zika virus infection

et al. 2019

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Section: Discussionmentioning

confidence: 99%

IL-1 receptor antagonist therapy mitigates placental dysfunction and perinatal injury following Zika virus infection

et al. 2019

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“…The frequency of Guillain-Barré syndrome is estimated to be 1/5,000 cases Lessler et al, 2016). Congenital malformations and adverse outcomes associated with ZIKV acquisition during pregnancy are likely due to placental infection and viral transmission to the fetus, with the virus displaying a tropism for neuronal cells (Garcez et al, 2016;Miner et al, 2016;Nowakowski et al, 2016;Quicke et al, 2016;Tang et al, 2016). However, ZIKV infection is generally asymptomatic or, in about 20% of the cases, associated with mild and non-specific symptoms (Lessler et al, 2016;Petersen et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells

et al. 2017

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The cytopathic effects of Zika virus (ZIKV) are poorly characterized. Innate immunity controls ZIKV infection and disease in most infected patients through mechanisms that remain to be understood. Here, we studied the morphological cellular changes induced by ZIKV and addressed the role of interferon-induced transmembrane proteins (IFITM), a family of broad-spectrum antiviral factors, during viral replication. We report that ZIKV induces massive vacuolization followed by "implosive" cell death in human epithelial cells, primary skin fibroblasts and astrocytes, a phenomenon which is exacerbated when IFITM3 levels are low. It is reminiscent of paraptosis, a caspase-independent, non-apoptotic form of cell death associated with the formation of large cytoplasmic vacuoles. We further show that ZIKV-induced vacuoles are derived from the endoplasmic reticulum (ER) and dependent on the PI3K/Akt signaling axis. Inhibiting the Sec61 ER translocon in ZIKV-infected cells blocked vacuole formation and viral production. Our results provide mechanistic insight behind the ZIKV-induced cytopathic effect and indicate that IFITM3, by acting as a gatekeeper for incoming virus, restricts virus takeover of the ER and subsequent cell death.

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“…Most notable are microcephaly and other congenital defects in infants born to mothers infected with ZIKV during pregnancy (Mlakar et al, 2016;Petersen et al, 2016;Rasmussen et al, 2016;Wikan and Smith, 2016). Although the exact mech-anism of neuropathogenesis remains uncertain, clinical abnormalities have been linked to the aberrant development and loss of neural progenitor cells (NPCs) (Cugola et al, 2016;Gabriel et al, 2017;Garcez et al, 2016;Li et al, 2016aLi et al, , 2016bTang et al, 2016). The contemporary strain of ZIKV has enhanced replication capacity and a specialized tropism for NPCs (Cugola et al, 2016;Dang et al, 2016;Garcez et al, 2016;Li et al, 2016b;Tang et al, 2016), although other types of cells are susceptible (Tabata et al, 2016;Weisblum et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos

Gao

et al. 2018

Cell Reports

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Zika virus (ZIKV) is a mosquito-transmitted flavivirus that is generally benign in humans. However, an emergent strain of ZIKV has become widespread, causing severe pre- and post-natal neurological defects. There is now an urgent need for prophylactic and therapeutic agents. To address this, we investigated six human monoclonal antibodies with ZIKV epitope specificity and neutralizing activity in mouse models of ZIKV infection and microcephaly. A single intraperitoneal injection of these antibodies conveyed distinct levels of adult and in utero protection from ZIKV infection, which closely mirrored their respective in vitro neutralizing activities. One antibody, ZK2B10, showed the most potent neutralization activity, completely protected uninfected mice, and markedly reduced tissue pathology in infected mice. Thus, ZK2B10 is a promising candidate for the development of antibody-based interventions and informs the rational design of ZIKV vaccine.

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Zika virus impairs growth in human neurospheres and brain organoids

Cited by 75 publications

References 1 publication

IL-1 receptor antagonist therapy mitigates placental dysfunction and perinatal injury following Zika virus infection

IL-1 receptor antagonist therapy mitigates placental dysfunction and perinatal injury following Zika virus infection

Zika virus induces massive cytoplasmic vacuolization and paraptosis‐like death in infected cells

A Single Injection of Human Neutralizing Antibody Protects against Zika Virus Infection and Microcephaly in Developing Mouse Embryos

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