scholarly journals Zika Virus Enters Soma of Neuron through NGF/TrkA-Like Endosomal Signaling Pathway

2021 ◽  
Author(s):  
wenzhong liu ◽  
hualan li
Keyword(s):  
Zika Virus ◽  
Neurological Disease ◽  
Search Strategy ◽  
Neuronal Cell ◽  
Glycoprotein E ◽  
Neuronal Soma ◽  
Neuron Cell Body ◽  
Endosomal Signaling ◽  
Congenital Zika Syndrome ◽  
Interaction With Receptors

Infection with the Zika virus results in severe neurological disease in adults or congenital Zika syndrome in newborns. We employed the domain search strategy to study the Zika virus glycoprotein E in this work. The results revealed that immature E contains a NGF domain (“MNKCYIQIMDLGHMCDATMSYECPMLDEGVEPDDVDCWCNTTSTWVVYGTCHH”) and is capable of interacting with TrkA. The E/TrkA complex increased E's interaction with receptors such as Axl and facilitated Zika virus endocytosis via clathrin. Rab5 retrograded transmission of Zika virus-containing E/TrkA endosomal signals to neuronal soma. Rab7 helped dissociation of E/TrkA in late acidic endosomes, and then E became mature after the NGF domain was cut. After membrane fusion with the endosome, the Zika virus was released into the neuron cell body. It showed only the immature E protein of Zika had NGF activity. The retrograde trafficking of endosomal signals (E/TrkA) similar to NGF/TrkA enabled Zika virus to infect neuronal cells. E's interference with the TrkA signal impaired neuronal cell growth and results in neuronal cell apoptosis.

scholarly journals Global RNAseq of ocular cells reveals gene dysregulation in both asymptomatic and with Congenital Zika Syndrome infants exposed prenatally to Zika virus

2020 ◽  
Author(s):  
Livia Rosa-Fernandes ◽  
Amina Bedrat ◽  
Maria Luiza B. dos Santos ◽  
Ana Pinto ◽  
E Lucena ◽  
...  
Keyword(s):  
Gene Expression ◽  
Zika Virus ◽  
Clinical Signs ◽  
Neuronal Cell ◽  
Embryonic Cells ◽  
Zikv Infection ◽  
Gene Dysregulation ◽  
Congenital Zika Syndrome ◽  
Invasive Method ◽  
And Control

AbstractIn 2015, Brazil reported an outbreak identified as Zika virus (ZIKV) infection associated with congenital abnormalities. To date, a total of 86 countries and territories have described evidence of Zika infection and recently the appearance of the African ZIKV lineage in Brazil highlights the risk of a new epidemic. The spectrum of ZIKV infection-induced alterations at both cellular and molecular levels is not completely elucidated. Here, we present for the first time the gene expression responses associated with prenatal ZIKV infection from ocular cells. We applied a recently developed non-invasive method (impression cytology) which use eye cells as a model for ZIKV studies. The ocular profiling revealed significant differences between exposed and control groups, as well as a different pattern in ocular transcripts from Congenital Zika Syndrome (CZS) compared to ZIKV-exposed but asymptomatic infants. Our data showed pathways related to mismatch repair, cancer, and PI3K/AKT/mTOR signaling and genes probably causative or protective in the modulation of ZIKV infection. Ocular cells revealed the effects of ZIKV infection on primordial neuronal cell genes, evidenced by changes in genes associated with embryonic cells. The changes in gene expression support an association with the gestational period of the infection and provide evidence for the resulting clinical and ophthalmological pathologies. Additionally, the findings of cell death- and cancer-associated deregulated genes raise concerns about the early onset of other potential pathologies including the need for tumor surveillance. Our results thus provide direct evidence that infants exposed prenatally to the Zika virus, not only with CZS but also without clinical signs (asymptomatic) express cellular and molecular changes with potential clinical implications.

scholarly journals Association between Genetic Variants in NOS2 and TNF Genes with Congenital Zika Syndrome and Severe Microcephaly

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 325
Author(s):  
Julia A. Gomes ◽  
Eduarda Sgarioni ◽  
Juliano A. Boquett ◽  
Ana Cláudia P. Terças-Trettel ◽  
Juliana H. da Silva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Zika Virus ◽  
Genetic Variants ◽  
Educational Level ◽  
Congenital Anomalies ◽  
Family Income ◽  
First Trimester ◽  
In Utero ◽  
Zikv Infection ◽  
Congenital Zika Syndrome

Zika virus (ZIKV) causes Congenital Zika Syndrome (CZS) in individuals exposed prenatally. Here, we investigated polymorphisms in VEGFA, PTGS2, NOS3, TNF, and NOS2 genes as risk factors to CZS. Forty children with CZS and forty-eight children who were in utero exposed to ZIKV infection, but born without congenital anomalies, were evaluated. Children with CZS were predominantly infected by ZIKV in the first trimester (p < 0.001) and had mothers with lower educational level (p < 0.001) and family income (p < 0.001). We found higher risk of CZS due the allele rs2297518[A] of NOS2 (OR = 2.28, CI 95% 1.17–4.50, p = 0.015). T allele and TT/CT genotypes of the TNF rs1799724 and haplotypes associated with higher expression of TNF were more prevalent in children with CZS and severe microcephaly (p = 0.029, p = 0.041 and p = 0.030, respectively). Our findings showed higher risk of CZS due ZIKV infection in the first trimester and suggested that polymorphisms in NOS2 and TNF genes affect the risk of CZS and severe microcephaly.

scholarly journals Dual burden of Zika and COVID-19 in India: challenges, opportunities and recommendations

2021 ◽  
Vol 49 (1) ◽  
Author(s):  
Mainak Bardhan ◽  
Debolina Pramanik ◽  
Rizana Riyaz ◽  
Mohammad Mehedi Hasan ◽  
Mohammad Yasir Essar
Keyword(s):  
Public Health ◽  
Early Diagnosis ◽  
Zika Virus ◽  
Virus Disease ◽  
Healthcare Resources ◽  
Health Measures ◽  
The World ◽  
Significant Public Health ◽  
Congenital Zika Syndrome ◽  
Dual Burden

AbstractThe COVID-19 pandemic has wreaked havoc in the world from last year, and any further insults like Zika virus will surely bring the apocalypse unto us. In July 2021, Zika began spreading in India, mainly in the state of Kerala. Zika infection resembles closely COVID-19 and other arboviral infections, which might lead to delayed and misdiagnosis, further leading to underreporting of cases. Some of the feared complications of Zika include Guillain–Barré syndrome and congenital Zika syndrome leading to microcephaly. Thus, Zika virus disease (ZVD) has significant public health and social impacts. Since the trifecta of infectious diseases (host, agent and environment) are all conducive to the spread of Zika in India, there is a huge risk that ZVD might become endemic in India, which is especially dangerous in the backdrop of this pandemic. This has to be stopped at all costs: the main aspects of which are public health measures, vector control and early diagnosis, especially in case of pregnant women. The diversion of healthcare resources for this pandemic has albeit made this difficult, but we must do our bit if we have to overcome this situation.

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 Drug-Screening Strategies for Inhibition of Virus-Induced Neuronal Cell Death

Viruses ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2317
Author(s):  
Durbadal Ojha ◽  
Tyson A. Woods ◽  
Karin E. Peterson
Keyword(s):  
Cell Death ◽  
Cell Lines ◽  
Zika Virus ◽  
Treatment Options ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Virus Production ◽  
Neuronal Stem Cell ◽  
Stem Cell Lines ◽  
Simplex Virus

A number of viruses, including Herpes Simplex Virus (HSV), West Nile Virus (WNV), La Crosse Virus (LACV), Zika virus (ZIKV) and Tick-borne encephalitis virus (TBEV), have the ability to gain access to the central nervous system (CNS) and cause severe neurological disease or death. Although encephalitis cases caused by these viruses are generally rare, there are relatively few treatment options available for patients with viral encephalitis other than palliative care. Many of these viruses directly infect neurons and can cause neuronal death. Thus, there is the need for the identification of useful therapeutic compounds that can inhibit virus replication in neurons or inhibit virus-induced neuronal cell death. In this paper, we describe the methodology to test compounds for their ability to inhibit virus-induced neuronal cell death. These protocols include the isolation and culturing of primary neurons; the culturing of neuroblastoma and neuronal stem cell lines; infection of these cells with viruses; treatment of these cells with selected drugs; measuring virus-induced cell death using MTT or XTT reagents; analysis of virus production from these cells; as well as the basic understanding in mode of action. We further show direct evidence of the effectiveness of these protocols by utilizing them to test the effectiveness of the polyphenol drug, Rottlerin, at inhibiting Zika virus infection and death of neuronal cell lines.

scholarly journals Asymptomatic Prenatal Zika Virus Infection and Congenital Zika Syndrome

2018 ◽  
Vol 5 (4) ◽  
Author(s):  
Enny S Paixao ◽  
Wei-Yee Leong ◽  
Laura C Rodrigues ◽  
Annelies Wilder-Smith
Keyword(s):  
Virus Infection ◽  
Birth Defects ◽  
Prospective Studies ◽  
Zika Virus ◽  
Retrospective Studies ◽  
Recall Bias ◽  
Virus Infections ◽  
Fetal Outcomes ◽  
Zika Virus Infection ◽  
Congenital Zika Syndrome

Abstract To investigate to what extent asymptomatic vs symptomatic prenatal Zika virus infections contribute to birth defects, we identified 3 prospective and 8 retrospective studies. The ratio varied greatly in the retrospective studies, most likely due to recruitment and recall bias. The prospective studies revealed a ratio of 1:1 for asymptomatic vs symptomatic maternal Zika infections resulting in adverse fetal outcomes.

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