scholarly journals High-throughput fitness profiling of Zika virus E protein reveals different roles for N-linked glycosylation during infection of mammalian and mosquito cells

2017 ◽  
Author(s):  
Danyang Gong ◽  
Tian-hao Zhang ◽  
Dawei Zhao ◽  
Yushen Du ◽  
Travis J. Chapa ◽  
...  
Keyword(s):  
Zika Virus ◽  
Cell Receptor ◽  
Human Cells ◽  
Nucleotide Position ◽  
List Type ◽  
Zikv Infection ◽  
E Protein ◽  
Mosquito Cells ◽  
Viral Mutant ◽  
Replication Fitness

AbstractZika virus (ZIKV) infection causes Guillain-Barré syndrome and severe birth defects. ZIKV envelope (E) protein is the major viral protein involved in cell receptor binding and entry and therefore considered one of the major determinants in ZIKV pathogenesis. Here, we report a gene-wide mapping of functional residues of ZIKV E protein using a mutant library with changes covering every nucleotide position. By comparing the replication fitness of every viral mutant between mosquito and human cells, we identified that mutations affecting N-linked glycosylation at N154 position display the most divergence. Through characterizing individual mutants, we show that, while ablation of N-linked glycosylation selectively benefits ZIKV infection of mosquito cells by enhancing cell entry, it either had little impact on ZIKV infection on certain human cells or decreased infection through entry factor DC-SIGN. In conclusion, we define the roles of individual residues of ZIKV envelope protein, which contribute to ZIKV replication fitness in human and mosquito cells.HighlightsGene-wide mapping of functional residues of E protein in human and mosquito cells.Mutations affecting N-linked glycosylation display the most dramatic difference.N-linked glycosylation decreases ZIKV entry into mosquito cells.N-linked glycosylation is important for DC-SIGN mediated infection of human cells.

scholarly journals The Envelope Residues E152/156/158 of Zika Virus Influence the Early Stages of Virus Infection in Human Cells

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1444 ◽  
Author(s):  
Sandra Bos ◽  
Wildriss Viranaicken ◽  
Etienne Frumence ◽  
Ge Li ◽  
Philippe Desprès ◽  
...  
Keyword(s):  
Viral Infection ◽  
Zika Virus ◽  
Molecular Mechanisms ◽  
Pacific Islands ◽  
Human Cells ◽  
Host Cells ◽  
Zikv Infection ◽  
Viral Attachment ◽  
Human Host ◽  
E Protein

Emerging infections of mosquito-borne Zika virus (ZIKV) pose an increasing threat to human health, as documented over the recent years in South Pacific islands and the Americas in recent years. To better understand molecular mechanisms underlying the increase in human cases with severe pathologies, we recently demonstrated the functional roles of structural proteins capsid (C), pre-membrane (prM), and envelop (E) of ZIKV epidemic strains with the initiation of viral infection in human cells. Specifically, we found that the C-prM region contributes to permissiveness of human host cells to ZIKV infection and ZIKV-induced cytopathic effects, whereas the E protein is associated with viral attachment and early infection. In the present study, we further characterize ZIKV E proteins by investigating the roles of residues isoleucine 152 (Ile152), threonine 156 (Thr156), and histidine 158 (His158) (i.e., the E-152/156/158 residues), which surround a unique N-glycosylation site (E-154), in permissiveness of human host cells to epidemic ZIKV infection. For comparison purpose, we generated mutant molecular clones of epidemic BeH819015 (BR15) and historical MR766-NIID (MR766) strains that carry each other’s E-152/156/158 residues, respectively. We observed that the BR15 mutant containing the E-152/156/158 residues from MR766 was less infectious in A549-Dual™ cells than parental virus. In contrast, the MR766 mutant containing E-152/156/158 residues from BR15 displayed increased infectivity. The observed differences in infectivity were, however, not correlated with changes in viral binding onto host-cells or cellular responses to viral infection. Instead, the E-152/156/158 residues from BR15 were associated with an increased efficiency of viral membrane fusion inside infected cells due to conformational changes of E protein that enhance exposure of the fusion loop. Our data highlight an important contribution of E-152/156/158 residues to the early steps of ZIKV infection in human cells.

scholarly journals Analysis of Zika virus capsid-Aedes aegypti mosquito interactome reveals pro-viral host factors critical for establishing infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rommel J. Gestuveo ◽  
Jamie Royle ◽  
Claire L. Donald ◽  
Douglas J. Lamont ◽  
Edward C. Hutchinson ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Protein Interactions ◽  
Zika Virus ◽  
Label Free ◽  
Protein Protein Interactions ◽  
Zikv Infection ◽  
Ubiquitin Protein Ligase ◽  
Mosquito Cells ◽  
Endoplasmic Reticulum Protein ◽  
Arboviral Diseases

AbstractThe escalating global prevalence of arboviral diseases emphasizes the need to improve our understanding of their biology. Research in this area has been hindered by the lack of molecular tools for studying virus-mosquito interactions. Here, we develop an Aedes aegypti cell line which stably expresses Zika virus (ZIKV) capsid proteins in order to study virus-vector protein-protein interactions through quantitative label-free proteomics. We identify 157 interactors and show that eight have potentially pro-viral activity during ZIKV infection in mosquito cells. Notably, silencing of transitional endoplasmic reticulum protein TER94 prevents ZIKV capsid degradation and significantly reduces viral replication. Similar results are observed if the TER94 ortholog (VCP) functioning is blocked with inhibitors in human cells. In addition, we show that an E3 ubiquitin-protein ligase, UBR5, mediates the interaction between TER94 and ZIKV capsid. Our study demonstrates a pro-viral function for TER94/VCP during ZIKV infection that is conserved between human and mosquito cells.

scholarly journals Ayapana triplinervis Essential Oil and Its Main Component Thymohydroquinone Dimethyl Ether Inhibit Zika Virus at Doses Devoid of Toxicity in Zebrafish

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3447 ◽  
Author(s):  
Juliano G. Haddad ◽  
Morgane Picard ◽  
Sebastien Bénard ◽  
Claire Desvignes ◽  
Philippe Desprès ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Acute Toxicity ◽  
Essential Oil ◽  
Dimethyl Ether ◽  
Zika Virus ◽  
Human Cells ◽  
Reunion Island ◽  
Zikv Infection ◽  
Réunion Island ◽  
Main Component

Zika virus (ZIKV) is an emerging mosquito-borne virus of medical concern. ZIKV infection may represent a serious disease, causing neonatal microcephaly and neurological disorders. Nowadays, there is no approved antiviral against ZIKV. Several indigenous or endemic medicinal plants from Mascarene archipelago in Indian Ocean have been found able to inhibit ZIKV infection. The purpose of our study was to determine whether essential oil (EO) from Reunion Island medicinal plant Ayapana triplinervis, whose thymohydroquinone dimethyl ether (THQ) is the main component has the potential to prevent ZIKV infection in human cells. Virological assays were performed on human epithelial A549 cells infected with either GFP reporter ZIKV or epidemic viral strain. Zebrafish assay was employed to evaluate the acute toxicity of THQ in vivo. We showed that both EO and THQ inhibit ZIKV infection in human cells with IC50 values of 38 and 45 µg/mL, respectively. At the noncytotoxic concentrations, EO and THQ reduced virus progeny production by 3-log. Time-of-drug-addition assays revealed that THQ could act as viral entry inhibitor. At the antiviral effective concentration, THQ injection in zebrafish does not lead to any signs of stress and does not impact fish survival, demonstrating the absence of acute toxicity for THQ. From our data, we propose that THQ is a new potent antiviral phytocompound against ZIKV, supporting the potential use of medicinal plants from Reunion Island as a source of natural and safe antiviral substances against medically important mosquito-borne viruses.

scholarly journals High-Throughput Fitness Profiling of Zika Virus E Protein Reveals Different Roles for Glycosylation during Infection of Mammalian and Mosquito Cells

iScience ◽  
2018 ◽  
Vol 1 ◽  
pp. 97-111 ◽  
Author(s):  
Danyang Gong ◽  
Tian-Hao Zhang ◽  
Dawei Zhao ◽  
Yushen Du ◽  
Travis J. Chapa ◽  
...  
Keyword(s):  
High Throughput ◽  
Zika Virus ◽  
E Protein ◽  
Mosquito Cells

scholarly journals Rearrangement of Actin Cytoskeleton by Zika Virus Infection Facilitates Blood–Testis Barrier Hyperpermeability

2021 ◽  
Author(s):  
Yiwen Nie ◽  
Lixia Hui ◽  
Moujian Guo ◽  
Wei Yang ◽  
Rui Huang ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Zika Virus ◽  
Actin Filaments ◽  
Protein Domain ◽  
Cell Periphery ◽  
Zikv Infection ◽  
E Protein ◽  
Junction Protein ◽  
Blood Testis Barrier

AbstractIn recent years, various serious diseases caused by Zika virus (ZIKV) have made it impossible to be ignored. Confirmed existence of ZIKV in semen and sexually transmission of ZIKV suggested that it can break the blood–testis barrier (BTB), or Sertoli cell barrier (SCB). However, little is known about the underlying mechanism. In this study, interaction between actin, an important component of the SCB, and ZIKV envelope (E) protein domain III (EDIII) was inferred from co-immunoprecipitation (Co-IP) liquid chromatography–tandem mass spectrometry (LC–MS/MS) analysis. Confocal microscopy confirmed the role of actin filaments (F-actin) in ZIKV infection, during which part of the stress fibers, the bundles that constituted by paralleled actin filaments, were disrupted and presented in the cell periphery. Colocalization of E and reorganized actin filaments in the cell periphery of transfected Sertoli cells suggests a participation of ZIKV E protein in ZIKV-induced F-actin rearrangement. Perturbation of F-actin by cytochalasin D (CytoD) or Jasplakinolide (Jas) enhanced the infection of ZIKV. More importantly, the transepithelial electrical resistance (TEER) of an in vitro mouse SCB (mSCB) model declined with the progression of ZIKV infection or overexpression of E protein. Co-IP and confocal microscopy analyses revealed that the interaction between F-actin and tight junction protein ZO-1 was reduced after ZIKV infection or E protein overexpression, highlighting the role of E protein in ZIKV-induced disruption of the BTB. We conclude that the interaction between ZIKV E and F-actin leads to the reorganization of F-actin network, thereby compromising BTB integrity.

scholarly journals Brevinin-2GHk, a Peptide Derived from the Skin of Fejervarya limnocharis, Inhibits Zika Virus Infection by Disrupting Viral Integrity

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2382
Author(s):  
Weichen Xiong ◽  
Jingyan Li ◽  
Yifei Feng ◽  
Jinwei Chai ◽  
Jiena Wu ◽  
...  
Keyword(s):  
Zika Virus ◽  
Lead Compound ◽  
Zikv Infection ◽  
Middle Stage ◽  
E Protein ◽  
Antiviral Effects ◽  
Effective Drugs ◽  
Further Development ◽  
Weak Antibacterial Activity ◽  
Fejervarya Limnocharis

Several years have passed since the Zika virus (ZIKV) pandemic reoccurred in 2015–2016. However, there is still a lack of proved protective vaccines or effective drugs against ZIKV. The peptide brevinin-2GHk (BR2GK), pertaining to the brevinin-2 family of antimicrobial peptides, has been reported to exhibit only weak antibacterial activity, and its antiviral effects have not been investigated. Thus, we analyzed the effect of BR2GK on ZIKV infection. BR2GK showed significant inhibitory activity in the early and middle stages of ZIKV infection, with negligible cytotoxicity. Furthermore, BR2GK was suggested to bind with ZIKV E protein and disrupt the integrity of the envelope, thus directly inactivating ZIKV. In addition, BR2GK can also penetrate the cell membrane, which may contribute to inhibition of the middle stage of ZIKV infection. BR2GK blocked ZIKV E protein expression with an IC50 of 3.408 ± 0.738 μΜ. In summary, BR2GK was found to be a multi-functional candidate and a potential lead compound for further development of anti-ZIKV drugs.

Vertical transmission of Zika virus (ZIKV) in early pregnancy: two cases, two different courses

2016 ◽  
Vol 5 (2) ◽  
pp. 131-133 ◽  
Author(s):  
Kimberly Herrera ◽  
James Bernasko ◽  
David Garry ◽  
Sevan Vahanian ◽  
Cynthia Kaplan
Keyword(s):  
Amniotic Fluid ◽  
Early Pregnancy ◽  
Zika Virus ◽  
Pregnancy Termination ◽  
List Type ◽  
Rt Pcr ◽  
Zikv Infection ◽  
Maternal Illness ◽  
Fetal Serum ◽  
Polymerase Chain

Abstract Background: Vertical Zika virus (ZIKV) transmission is actively being studied. Prior cases of ZIKV in pregnancy have suggested an association with infection and adverse fetal outcomes. We describe two cases of maternal illness and their respective pregnancy courses. Case 1: A 30-year-old Hispanic female presented with rash, fatigue, and chills after noticing mosquito bites in Honduras. Fetal anatomy appeared normal on ultrasound at 16 and 17 weeks. ZIKV RNA reverse-transcriptase-polymerase-chain-reaction (RT-PCR) was identified in her serum and amniotic fluid. She opted for pregnancy termination. Fetal serum and tissue analysis confirmed ZIKV infection. Case 2: A 28-year-old Hispanic female presented with rash, fever, and fatigue after sexual intercourse. Her ZIKV serum RNA RT-PCR was positive and amniotic fluid was negative. Fetal anatomy appeared normal at 20 and 22 weeks and her pregnancy remains ongoing. Conclusion: The effects of maternal ZIKV infection in early pregnancy can vary.

scholarly journals Gut microbiota modulation induced by Zika virus infection in immunocompetent mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rafael Corrêa ◽  
Igor de Oliveira Santos ◽  
Heloísa Antoniella Braz-de-Melo ◽  
Lívia Pimentel de Sant’Ana ◽  
Raquel das Neves Almeida ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Zika Virus ◽  
Hypervariable Region ◽  
Microbiota Composition ◽  
Colon Tissue ◽  
Zikv Infection ◽  
Immunological Responses ◽  
Immunocompetent Mice ◽  
Gut Microbiota Composition

AbstractGut microbiota composition can modulate neuroendocrine function, inflammation, and cellular and immunological responses against different pathogens, including viruses. Zika virus (ZIKV) can infect adult immunocompetent individuals and trigger brain damage and antiviral responses. However, it is not known whether ZIKV infection could impact the gut microbiome from adult immunocompetent mice. Here, we investigated modifications induced by ZIKV infection in the gut microbiome of immunocompetent C57BL/6J mice. Adult C57BL/6J mice were infected with ZIKV and the gut microbiota composition was analyzed by next-generation sequencing of the V4 hypervariable region present in the bacterial 16S rDNA gene. Our data showed that ZIKV infection triggered a significant decrease in the bacteria belonging to Actinobacteria and Firmicutes phyla, and increased Deferribacteres and Spirochaetes phyla components compared to uninfected mice. Interestingly, ZIKV infection triggered a significant increase in the abundance of bacteria from the Spirochaetaceae family in the gut microbiota. Lastly, we demonstrated that modulation of microbiota induced by ZIKV infection may lead to intestinal epithelium damage and intense leukocyte recruitment to the intestinal mucosa. Taken together, our data demonstrate that ZIKV infection can impact the gut microbiota composition and colon tissue homeostasis in adult immunocompetent mice.

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.

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