scholarly journals A single mutation in the prM protein of Zika virus contributes to fetal microcephaly

Science ◽  
2017 ◽  
Vol 358 (6365) ◽  
pp. 933-936 ◽  
Author(s):  
Ling Yuan ◽  
Xing-Yao Huang ◽  
Zhong-Yu Liu ◽  
Feng Zhang ◽  
Xing-Liang Zhu ◽  
...  
Keyword(s):  
Zika Virus ◽  
Neural Progenitor Cells ◽  
French Polynesia ◽  
Causal Link ◽  
Evolutionary Analysis ◽  
Single Mutation ◽  
Mouse Fetus ◽  
Viral Polyprotein ◽  
Human And Mouse ◽  
Human Npcs

Zika virus (ZIKV) has evolved into a global health threat because of its unexpected causal link to microcephaly. Phylogenetic analysis reveals that contemporary epidemic strains have accumulated multiple substitutions from their Asian ancestor. Here we show that a single serine-to-asparagine substitution [Ser139→Asn139 (S139N)] in the viral polyprotein substantially increased ZIKV infectivity in both human and mouse neural progenitor cells (NPCs) and led to more severe microcephaly in the mouse fetus, as well as higher mortality rates in neonatal mice. Evolutionary analysis indicates that the S139N substitution arose before the 2013 outbreak in French Polynesia and has been stably maintained during subsequent spread to the Americas. This functional adaption makes ZIKV more virulent to human NPCs, thus contributing to the increased incidence of microcephaly in recent ZIKV epidemics.

scholarly journals Zika Virus and Neuropathogenesis: The Unanswered Question of Which Strain Is More Prone to Causing Microcephaly and Other Neurological Defects

2021 ◽  
Vol 15 ◽  
Author(s):  
Emily Louise King ◽  
Nerea Irigoyen
Keyword(s):  
Cerebral Cortex ◽  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
French Polynesia ◽  
Cellular Processes ◽  
Neurotropic Viruses ◽  
Congenital Zika Syndrome ◽  
Induced Apoptosis

Despite being perceived to be a relatively innocuous pathogen during its circulation in Africa in the 20th century, consequent outbreaks in French Polynesia and Latin America revealed the Zika virus (ZIKV) to be capable of causing severe neurological defects. Foetuses infected with the virus during pregnancy developed a range of pathologies including microcephaly, cerebral calcifications and macular scarring. These are now collectively known as Congenital Zika syndrome (CZS). It has been established that the neuropathogenesis of ZIKV results from infection of neural progenitor cells in the developing cerebral cortex. Following this, two main hypotheses have emerged: the virus causes either apoptosis or premature differentiation of neural progenitor cells, reducing the final number of mature neurons in the cerebral cortex. This review describes the cellular processes which could potentially cause virus induced apoptosis or premature differentiation, leading to speculation that a combination of the two may be responsible for the pathologies associated with ZIKV. The review also discusses which specific lineages of the ZIKV can employ these mechanisms. It has been unclear in the past whether the virus evolved its neurotropic capability following circulation in Africa, or if the virus has always caused microcephaly but public health surveillance in Africa had failed to detect it. Understanding the true neuropathogenesis of ZIKV is key to being prepared for further outbreaks in the future, and it will also provide insight into how neurotropic viruses can cause profound and life-long neurological defects.

Inhibition of Neurogenesis by Zika Virus Infection

2018 ◽  
Vol 17 (2) ◽  
pp. 78-86 ◽  
Author(s):  
Fahim Ahmad ◽  
Amna Siddiqui ◽  
Mohammad A. Kamal ◽  
Sayed Sartaj Sohrab
Keyword(s):  
Zika Virus ◽  
Molecular Mechanisms ◽  
Neural Progenitor Cells ◽  
Management Strategies ◽  
Neuronal Cell ◽  
The United States ◽  
Causal Link ◽  
Published Data ◽  
Zikv Infection ◽  
First Case

Background & Objective: The link between Zika Virus (ZIKV) epidemic and neurological disorder has raised an urgent global alarm. The current epidemic of ZIKV has triggered quick responses in the scientific world. The first case of ZIKV was reported in 2015 from Brazil and now has spread over 30 countries. Nearly four hundred cases of traveler associated ZIKV infection have also been reported in the United States. ZIKV is primarily transmitted by mosquito belonging to the genus Aedes that are widely distributed throughout the world. Additionally, the virus can also be transmitted from male to female by sexual contact. The epidemiological investigations during the current outbreak found a causal link between infection in pregnant women and the development of microcephaly (MCPH) in their unborn babies. This finding is a cause of grave concern since MCPH is a serious neural developmental disorder that can lead to significant post-natal developmental abnormalities and disabilities. Recently, published data indicates that ZIKV infection severely affects the growth of fetal neural progenitor cells and cerebral neurons resulting in malformation of cerebral cortex leading to MCPH. Recently, it has been reported that ZIKV infection deregulates the signaling pathway of neuronal cell and inhibits the neurogenesis. Conclusion: In this review, we discussed the information about cellular and molecular mechanisms of neurodegeneration of human neuronal cells and inhibition of neurogenesis. The provided information in this review will be very useful further not only in neuro-scientific research but also in the desig and development of management strategies for MCPH and other mosquito-borne diseases.

scholarly journals Transmission dynamics of Zika virus in island populations: a modelling analysis of the 2013-14 French Polynesia outbreak

2016 ◽  
Author(s):  
Adam J. Kucharski ◽  
Sebastian Funk ◽  
Rosalind M. Eggo ◽  
Henri-Pierre Mallet ◽  
W. John Edmunds ◽  
...  
Keyword(s):  
South America ◽  
Dengue Virus ◽  
Zika Virus ◽  
French Polynesia ◽  
Neurological Complications ◽  
Transmission Dynamics ◽  
Guillain Barre Syndrome ◽  
Island Populations ◽  
The Pacific ◽  
Guillain Barré

AbstractBetween October 2013 and April 2014, more than 30,000 cases of Zika virus (ZIKV) disease were estimated to have attended healthcare facilities in French Polynesia. ZIKV has also been reported in Africa and Asia, and in 2015 the virus spread to South America and the Caribbean. Infection with ZIKV has been associated with neurological complications including Guillain-Barré Syndrome (GBS) and microcephaly, which led the World Health Organization to declare a Public Health Emergency of International Concern in February 2015. To better understand the transmission dynamics of ZIKV, we used a mathematical model to examine the 2013–14 outbreak on the six major archipelagos of French Polynesia. Our median estimates for the basic reproduction number ranged from 2.6–4.8, with an estimated 11.5% (95% CI: 7.32–17.9%) of total infections reported. As a result, we estimated that 94% (95% CI: 91–97%) of the total population of the six archipelagos were infected during the outbreak. Based on the demography of French Polynesia, our results imply that if ZIKV infection provides complete protection against future infection, it would take 12–20 years before there are a sufficient number of susceptible individuals for ZIKV to reemerge, which is on the same timescale as the circulation of dengue virus serotypes in the region. Our analysis suggests that ZIKV may exhibit similar dynamics to dengue virus in island populations, with transmission characterized by large, sporadic outbreaks with a high proportion of asymptomatic or unreported cases.Author SummarySince the first reported major outbreak of Zika virus disease in Micronesia in 2007, the virus has caused outbreaks throughout the Pacific and South America. Transmitted by the Aedes species of mosquitoes, the virus has been linked to possible neurological complications including Guillain-Barre Syndrome and microcephaly. To improve our understanding of the transmission dynamics of Zika virus in island populations, we analysed the 2013–14 outbreak on the six major archipelagos of French Polynesia. We found evidence that Zika virus infected the majority of population, but only around 12% of total infections on the archipelagos were reported as cases. If infection with Zika virus generates lifelong immunity, we estimate that it would take at least 15–20 years before there are enough susceptible people for the virus to reemerge. Our results suggest that Zika virus could exhibit similar dynamics to dengue virus in the Pacific, producing large but sporadic outbreaks in small island populations.

scholarly journals Zika viruses of both African and Asian lineages cause fetal harm in a vertical transmission model

2018 ◽  
Author(s):  
Anna S. Jaeger ◽  
Reyes A. Murreita ◽  
Lea R. Goren ◽  
Chelsea M. Crooks ◽  
Ryan V. Moriarty ◽  
...  
Keyword(s):  
Mouse Model ◽  
Vertical Transmission ◽  
Birth Defects ◽  
Asian American ◽  
Zika Virus ◽  
French Polynesia ◽  
Transmission Model ◽  
Foreseeable Future ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

AbstractCongenital Zika virus (ZIKV) infection was first linked to birth defects during the American outbreak 1–3. It has been proposed that mutations unique to the Asian/American-genotype explain, at least in part, the ability of Asian/American ZIKV to cause congenital Zika syndrome (CZS) 4,5. Recent studies identified mutations in ZIKV infecting humans that arose coincident with the outbreak in French Polynesia and were stably maintained during subsequent spread to the Americas 5. Here we show that African ZIKV can infect and harm fetuses and that the S139N mutation that has been associated with the American outbreak is not essential for fetal harm. Our findings, in a vertical transmission mouse model, suggest that ZIKV will remain a threat to pregnant women for the foreseeable future, including in Africa, southeast Asia, and the Americas. Additional research is needed to better understand the risks associated with ZIKV infection during pregnancy, both in areas where the virus is newly endemic and where it has been circulating for decades.

scholarly journals Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barré syndrome: From systematic review to living systematic review

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 196 ◽  
Author(s):  
Michel Jacques Counotte ◽  
Dianne Egli-Gany ◽  
Maurane Riesen ◽  
Million Abraha ◽  
Teegwendé Valérie Porgo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Zika Virus ◽  
Congenital Abnormalities ◽  
Causal Link ◽  
The Body ◽  
Guillain Barre Syndrome ◽  
Sufficient Evidence ◽  
Zikv Infection ◽  
Guillain Barré Syndrome ◽  
Guillain Barré

Background. The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and Guillain-Barré syndrome (GBS). The World Health Organization stated that there is “sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS”. This conclusion was based on a systematic review of the evidence published until 30.05.2016. Since then, the body of evidence has grown substantially, leading to this update of that systematic review with new evidence published from 30.05.2016 – 18.01.2017, update 1. Methods. We review evidence on the causal link between ZIKV infection and adverse congenital outcomes and the causal link between ZIKV infection and GBS or immune-mediated thrombocytopaenia purpura. We also describe the transition of the review into a living systematic review, a review that is continually updated. Results. Between 30.05.2016 and 18.01.2017, we identified 2413 publications, of which 101 publications were included. The evidence added in this update confirms the conclusion of a causal association between ZIKV and adverse congenital outcomes. New findings expand the evidence base in the dimensions of biological plausibility, strength of association, animal experiments and specificity. For GBS, the body of evidence has grown during the search period for update 1, but only for dimensions that were already populated in the previous version. There is still a limited understanding of the biological pathways that potentially cause the occurrence of autoimmune disease following ZIKV infection. Conclusions. This systematic review confirms previous conclusions that ZIKV is a cause of congenital abnormalities, including microcephaly, and is a trigger of GBS. The transition to living systematic review techniques and methodology provides a proof of concept for the use of these methods to synthesise evidence about an emerging pathogen such as ZIKV.

scholarly journals Zika virus is transmitted in neural progenitor cells via cell-to-cell spread and infection is inhibited by the autophagy inducer trehalose

2020 ◽  
pp. JVI.02024-20
Author(s):  
Alex E Clark ◽  
Zhe Zhu ◽  
Florian Krach ◽  
Jeremy N Rich ◽  
Gene W. Yeo ◽  
...  
Keyword(s):  
Viral Replication ◽  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neutralizing Antibody ◽  
Neural Progenitor ◽  
Health Concern ◽  
Free Virus ◽  
Zikv Infection ◽  
Infected Cells

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes congenital Zika syndrome and neurological symptoms in some adults. There are currently no approved treatments or vaccines for ZIKV, and exploration of therapies targeting host processes could avoid viral development of drug resistance. The purpose of our study was to determine if the non-toxic and widely used disaccharide trehalose, which showed antiviral activity against Human Cytomegalovirus (HCMV) in our previous work, could restrict ZIKV infection in clinically relevant neural progenitor cells (NPCs). Trehalose is known to induce autophagy, the degradation and recycling of cellular components. Whether autophagy is proviral or antiviral for ZIKV is controversial and depends on cell type and specific conditions used to activate or inhibit autophagy. We show here that trehalose treatment of NPCs infected with recent ZIKV isolates from Panama and Puerto Rico significantly reduces viral replication and spread. In addition, we demonstrate that ZIKV infection in NPCs spreads primarily cell-to-cell as an expanding infectious center, and NPCs are infected via contact with infected cells far more efficiently than by cell-free virus. Importantly, ZIKV was able to spread in NPCs in the presence of neutralizing antibody.Importance Zika virus causes birth defects and can lead to neurological disease in adults. While infection rates are currently low, ZIKV remains a public health concern with no treatment or vaccine available. Targeting a cellular pathway to inhibit viral replication is a potential treatment strategy that avoids development of antiviral resistance. We demonstrate in this study that the non-toxic autophagy-inducing disaccharide trehalose reduces spread and output of ZIKV in infected neural progenitor cells (NPCs), the major cells infected in the fetus. We show that ZIKV spreads cell-to-cell in NPCs as an infectious center and that NPCs are more permissive to infection by contact with infected cells than by cell-free virus. We find that neutralizing antibody does not prevent the spread of the infection in NPCs. These results are significant in demonstrating anti-ZIKV activity of trehalose and in clarifying the primary means of Zika virus spread in clinically relevant target cells.

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