Anatomical, animal, and cellular evidence for Zika-induced pathogenesis of fetal microcephaly

Wang, Jing-Zhang; Guo, Xinhua; Xu, Dianguo

doi:10.1016/j.braindev.2016.10.012

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…HEK293 cells are ubiquitously used for many purposes 29 but can also be used for analysis of neuronal synapse formation 30 and has even been argued that HEK293 cells are of neuronal lineage 31 . Our accidental finding in HEK293 cells led to this investigation of the role of prM-Env in ZIKV induced neuronal apoptosis and further corroborates the relationship between ZIKV infection and neurological developmental disorders 13 , 14 , 26 .…”

Section: Discussionsupporting

confidence: 78%

“…The severe clinical symptoms caused by ZIKV infection have aroused world-wide attention. Significant breakthroughs and new questions have been made during the rapid attempt to understand the relationship between ZIKV and abnormal development of nervous system 15 , 25 , 26 . The neuronal apoptosis induced by ZIKV has been confirmed both in vitro 14 and in vivo 13 , 27 .…”

Section: Discussionmentioning

confidence: 99%

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Zika Virus Envelope Protein induces G2/M Cell Cycle Arrest and Apoptosis via an Intrinsic Cell Death Signaling Pathway in Neuroendocrine PC12 Cells

Liu¹,

Li²,

Li³

et al. 2018

Int. J. Biol. Sci.

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Clinical evidence suggests that there exists a strong correlation between Zika virus (ZIKV) infection and abnormal development of the nervous system. However, the underlying mechanisms remain to be elusive. In this study, recombinant lentiviral vectors coding for ZIKV structural proteins and truncations (prM-Env, M-Env and Env) were transduced into PC12 cells. Envelope (Env) overexpression induced significant inhibition of proliferation and triggered G2/M cell cycle arrest and apoptosis in PC12 cells. Flow cytometry and western blot analysis showed that the apoptosis was associated with up-regulation of both p53 and p21Cip1/Waf1 and down-regulation of cyclin B1. Presence of aberrant nuclei clusters were confirmed by immunofluorescence staining analysis. The data indicate that overexpression of prM-Env, M-Env or Env led to apoptosis via an intrinsic cell death signaling pathway that is dependent on the activation of caspase-9 and caspase-3 and accompanied by an increased ratio of Bax to Bcl-2 in transduced PC12 cells. In summary, our results suggest that ZIKV Env protein causes apoptosis in PC12 cells via an intrinsic cell death signaling pathway, which may contribute to ZIKV-induced abnormal development of the nervous system.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Zika Virus Envelope Protein induces G2/M Cell Cycle Arrest and Apoptosis via an Intrinsic Cell Death Signaling Pathway in Neuroendocrine PC12 Cells

Liu¹,

Li²,

Li³

et al. 2018

Int. J. Biol. Sci.

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“…Nowadays, the relationship between the occurrence of microcephaly in newborns and ZIKV has been established [ 29 ]. In this recently published review paper, the authors have highlighted the original experimental evidences that have strengthened the potential link between ZIKV and the high incidence of microcephaly in newborn babies.…”

Section: General Characteristics Of the Zikv And Its Infectivitymentioning

confidence: 99%

Sulfated Glycans and Related Digestive Enzymes in the Zika Virus Infectivity: Potential Mechanisms of Virus-Host Interaction and Perspectives in Drug Discovery

Pomin

2017

Interdisciplinary Perspectives on Infectious Diseases

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As broadly reported, there is an ongoing Zika virus (ZIKV) outbreak in countries of Latin America. Recent findings have demonstrated that ZIKV causes severe defects on the neural development in fetuses in utero and newborns. Very little is known about the molecular mechanisms involved in the ZIKV infectivity. Potential therapeutic agents are also under investigation. In this report, the possible mechanisms of action played by glycosaminoglycans (GAGs) displayed at the surface proteoglycans of host cells, and likely in charge of interactions with surface proteins of the ZIKV, are highlighted. As is common for the most viruses, these sulfated glycans serve as receptors for virus attachment onto the host cells and consequential entry during infection. The applications of (1) exogenous sulfated glycans of different origins and chemical structures capable of competing with the virus attachment receptors (supposedly GAGs) and (2) GAG-degrading enzymes able to digest the virus attachment receptors on the cells may be therapeutically beneficial as anti-ZIKV. This communication attempts, therefore, to offer some guidance for the future research programs aimed to unveil the molecular mechanisms underlying the ZIKV infectivity and to develop therapeutics capable of decreasing the devastating consequences caused by ZIKV outbreak in the Americas.

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Increased activity of unlinked Zika virus NS2B/NS3 protease compared to linked Zika virus protease

Kuiper

Slater

Spellmon

et al. 2017

Biochemical and Biophysical Research Communications

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Zika virus (ZIKV) is a flavivirus spread by daytime-active Aedes spp. mosquitoes such as A. aegypti and A. albopictus. Previously thought to be a mild infection, the latest ZIKV outbreak in the Americas is causally associated with more severe symptoms as well as severe birth defects, such as microcephaly. Currently no vaccine or antiviral exists. However, recent progress has demonstrated the viral NS2B/NS3 protease may be a suitable target for the development of small-molecule antiviral agents. To better understand the ZIKV protease, we expressed, purified, and characterized unlinked and linked NS2B/NS3 protease corresponding to an isolate from the recent outbreak in Puerto Rico. Unlinked ZIKV protease is more active and binds substrate with greater affinity than linked ZIKV protease. Therefore, we propose that unlinked ZIKV protease be used when evaluating or designing ZIKV protease inhibitors. Additionally, potent inhibitors of related viral proteases, like West Nile Virus and Dengue virus, may serve as advanced starting points to identify and develop ZIKV protease inhibitors.

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Anatomical, animal, and cellular evidence for Zika-induced pathogenesis of fetal microcephaly

Cited by 4 publications

References 19 publications

Zika Virus Envelope Protein induces G2/M Cell Cycle Arrest and Apoptosis via an Intrinsic Cell Death Signaling Pathway in Neuroendocrine PC12 Cells

Zika Virus Envelope Protein induces G2/M Cell Cycle Arrest and Apoptosis via an Intrinsic Cell Death Signaling Pathway in Neuroendocrine PC12 Cells

Sulfated Glycans and Related Digestive Enzymes in the Zika Virus Infectivity: Potential Mechanisms of Virus-Host Interaction and Perspectives in Drug Discovery

Increased activity of unlinked Zika virus NS2B/NS3 protease compared to linked Zika virus protease

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