Functional Analysis of Glycosylation of Zika Virus Envelope Protein

Fontes-Garfias, Camila R.; Shan, Chao; Luo, Huanle; Muruato, Antonio E.; Medeiros, Daniele Barbosa de Almeida; Mays, Elizabeth; Xie, Xuping; Zou, Jing; Roundy, Christopher M.; Wakamiya, Maki; Rossi, Shannan L.; Wang, Tian; Weaver, Scott C.; Shi, Pei–Yong

doi:10.1016/j.celrep.2017.10.016

Cited by 125 publications

(124 citation statements)

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“…Of note, N154 is a unique glycosylation site on Zika virus E protein, and it has been shown to support Zika virus infection in adult immune-deficient mice by either enhancing virus neuroinvasion or facilitating DC-SIGN binding (38, 39). However, when Zika virus was inoculated intracranially in neonatal mice, the deletion of N154 glycosylation had no impact on virus virulence (40). Collectively, these published data suggest that the N154D mutation may not be linked to the augmented infectivity and increased neurovirulce we have observed for the mouse adapted MA-SW01 virus.…”

Section: Resultsmentioning

confidence: 99%

“…In all four DENV serotypes, there are two highly conserved N-linked glycosylation sites on E protein, N67 and N153, that play critical role for viral entry (42). However, similar to West Nile virus (WNV) and Japanes encephalitis virus (JEV), Zika virus has only one N154 glycosylation site on E protein (40, 43). Indeed, glycosylation on N153 or N154 of E protein helps WNV or JEV to invade CNS in mammals (38,39,44,45).…”

Section: Discussionmentioning

confidence: 99%

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A single nonsynonymous mutation on gene encoding E protein of Zika virus leads to increased neurovirulencein vivo

Cheng

et al. 2020

Preprint

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Recent large outbreaks of Zika virus infection worldwide have revealed an 60 association between the viral infection and increased cases of specific 61 neurological problems including Congenital Zika Syndrome (including 62 microcephaly) and adult Guillain-Barré Syndrome. However, the determinants 63 of the increased neurovirulence of Zika virus remain uncertain. One hypothesis 64 is that some unique changes across the Zika viral genome have led to the 65 occurrence of these neurological diseases. To test this hypothesis, we 66 continuously propagated a clinical isolate of contemporary Zika virus (SW01) in 67 neonatal mice brain for 11 times to obtain an mouse central nervous system 68 (CNS) adapted Zika virus (MA-SW01) that showed significantly increased 69 neurovirulence in vivo. We then discovered that a single G to A nucleotide 70 substitution at the 1069 site of Zika virus open reading frame leading to a D 71 (aspartic acid) to N (asparagine) in viral Envelope protein is responsible for the 72 increased neurovirulence. These findings improve our understanding of the 73 neurological pathogenesis of Zika virus and provide clues for the development 74 of antiviral strategy. 75 76 77 78 79 80 81 82 83 84 85 86 87 5 / 32

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A single nonsynonymous mutation on gene encoding E protein of Zika virus leads to increased neurovirulencein vivo

Cheng

et al. 2020

Preprint

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“…This modification is involved in important viral replication and pathogenesis functions [42]. Mutagenesis studies on many flaviviruses, including the DENV, WNV and ZIKV, indicate that the loss of this N 153/154 -glycosylation impairs viral replication in the midgut [43–45]. Unlike most flaviviruses, the YFV Env lacks the N 153 / 154 -glycosylation canonical site.…”

Section: Resultsmentioning

confidence: 99%

Midgut barriers prevent the replication and dissemination of the yellow fever vaccine inAedes aegypti

Danet

Beauclair

Berthet

et al. 2019

Preprint

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20 Background 21 To be transmitted to vertebrate hosts via the saliva of their vectors, arthropod-borne viruses have 22 to cross several barriers in the mosquito body, including the midgut infection and escape barriers.23 Yellow fever virus (YFV) belongs to the genus Flavivirus, which includes human viruses transmitted 24 by Aedes mosquitoes, such as Dengue and Zika viruses. The live-attenuated YFV-17D vaccine has 25 been used safely and efficiently on a large scale since the end of World War II. Early studies have 26 shown, using viral titration from salivary glands of infected mosquitoes, that YFV-17D can infect 27 Aedes aegypti midgut, but does not disseminate to other tissues.28 Methodology/Principal Findings 29Here, we re-visited this issue using a panel of techniques, such as RT-qPCR, Western blot, 30 immunofluorescence and titration assays. We showed that YFV-17D replication was not efficient in 31Aedes aegypti midgut, as compared to the clinical isolate YFV-Dakar. Viruses that replicated in the 32 midgut failed to disseminate to secondary organs. When injected into the thorax of mosquitoes, 33 viruses succeeded in replicating into midgut-associated tissues, suggesting that, during natural 34 infection, the block for YFV-17D replication occurs at the basal membrane of the midgut. Our NGS 35 analysis revealed that YFV-Dakar genome exhibited a greater diversity than the vaccine strain; a trait 36 that may contribute to its ability to infect and disseminate efficiently in Ae. aegypti. 37 Conclusions/Significance 38The two barriers associated with Ae. aegypti midgut prevent YFV-17D replication. Our study 39 contributes to our basic understanding of vector-pathogen interactions and may also aid in the 40 development of non-transmissible live virus vaccines.41 42 3 43 Author summary 44 Most flaviviruses, including yellow fever virus (YFV), are transmitted between hosts by mosquito 45 bites. The yellow fever vaccine (YFV-17D) is one of the safest and most effective live virus vaccine 46 ever developed. It is also used as a platform for engineering vaccines against other health-threatening 47 flaviviruses, such as Japanese encephalitis, West Nile, Dengue and Zika viruses. We studied here the 48 replication and dissemination of YFV-17D in mosquitoes. Our data showed that YFV-17D replicates 49 poorly in mosquito midgut and is unable to disseminate to secondary organs, as compare to a YFV 50 clinical isolate. Our study contributes to our basic understanding of the interactions between viruses 51 and their vectors, which is key for conceiving new approaches in inhibiting virus transmission and 52 designing non-transmissible live virus vaccines. 53 54 Introduction 55 Arborviruses, which are transmitted among vertebrate hosts by blood-feeding arthropod vectors, 56 put billions of people at risk worldwide. Viral infection in arthropod is usually persistent. Following 57 uptake of an infectious blood meal by a female mosquito, arbovirus must initiate a productive 58 infection of the midgut epithelium, which consists of a ...

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“…ZIKV E protein glycosylation is dispensable for viral propagation in cell culture; however, this post-translational modification is necessary for robust ZIKV viral replication in mouse models and in mosquitos. 82,83 The group of S. Lok noted an insertion of an alanine residue at position 340 in ZIKV DIII that leads to differential positioning of DII and DIII and permits a hydrogen-bond network between five adjacent E proteins not seen in DENV2. 81 The authors conclude that this leads to a more compact structure for ZIKV, which could play a role in ZIKV tropism, transmission, and pathogenesis.…”

Section: Biochemistry and Molecular Biology Of Flavivirusesmentioning

confidence: 99%

Biochemistry and Molecular Biology of Flaviviruses

et al. 2018

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Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA–protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.

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Functional Analysis of Glycosylation of Zika Virus Envelope Protein

Cited by 125 publications

References 39 publications

A single nonsynonymous mutation on gene encoding E protein of Zika virus leads to increased neurovirulencein vivo

A single nonsynonymous mutation on gene encoding E protein of Zika virus leads to increased neurovirulencein vivo

Midgut barriers prevent the replication and dissemination of the yellow fever vaccine inAedes aegypti

Biochemistry and Molecular Biology of Flaviviruses

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