Structural insight into the Zika virus capsid encapsulating the viral genome

Li, Ting; Zhao, Qi; Yang, Xiaoyun; Chen, Cheng; Yang, Kailin; Wu, Chunlei; Zhang, Tianqing; Duan, Ying; Xue, Xu; Mi, Kaixia; Ji, Xiaoyun; Wang, Zefang; Yang, Haitao

doi:10.1038/s41422-018-0007-9

Cited by 25 publications

(29 citation statements)

References 12 publications

(19 reference statements)

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“…3c) showed helix α1 form the first layer interacting with the inner leaflet membrane, the second layer containing helices α2 and α3, and the third layer consists of the positively charged helix α4 that interact with the negatively charged RNA genome. Based on the position of helix α1, both our cryoEM ZIKV capsid and the crystal ZIKV capsid 6,7 structures are closer to that of the WNV capsid crystal structure (Supplementary Fig. 7b).…”

Section: Resultsmentioning

confidence: 53%

“…In all NMR and crystal structures of the recombinant flavivirus capsid protein [4][5][6][7] , only the residues from the N-terminal end to the end of helix α4 were expressed, as it was assumed to be the mature form of the capsid, i.e., after cleavage of α5 by NS2B/NS3 protease during processing of the single translated viral polyprotein (Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

“…Presently, it is believed that only the mature capsid protein, which consists of residues from its N terminus to the end of helix α4, are involved in flavivirus assembly. Thus, all available atomic resolution nuclear magnetic resonance (NMR) and crystal structures of isolated recombinant flavivirus capsid proteins reflect that truncated form: DENV (residues 21-100) 4 , WNV (residues 24-96) 5 , and ZIKV (residues 26-98) 6,7 , and also determined in the absence of lipids and viral RNA. This limits our understanding of how capsid interacts with the other components within the virus particle.…”

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confidence: 99%

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Capsid protein structure in Zika virus reveals the flavivirus assembly process

et al. 2020

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Structures of flavivirus (dengue virus and Zika virus) particles are known to near-atomic resolution and show detailed structure and arrangement of their surface proteins (E and prM in immature virus or M in mature virus). By contrast, the arrangement of the capsid proteins: RNA complex, which forms the core of the particle, is poorly understood, likely due to inherent dynamics. Here, we stabilize immature Zika virus via an antibody that binds across the E and prM proteins, resulting in a subnanometer resolution structure of capsid proteins within the virus particle. Fitting of the capsid protein into densities shows the presence of a helix previously thought to be removed via proteolysis. This structure illuminates capsid protein quaternary organization, including its orientation relative to the lipid membrane and the genomic RNA, and its interactions with the transmembrane regions of the surface proteins. Results show the capsid protein plays a central role in the flavivirus assembly process.

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Section: Resultsmentioning

confidence: 53%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Capsid protein structure in Zika virus reveals the flavivirus assembly process

et al. 2020

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“…Interestingly their studies indicated that ZIKV C bound all nucleic acids with affinities in the nanomolar range. This high affinity for all nucleic acids lends itself to the dsRNA binding ability which prevents dicer activity in mosquitos, as noted previously [48], and others have shown that ZIKV capsid's ability to bind ssDNA is made possible by the positively charged surface of the protein [49]. Although the affinity for all nucleic acids is high, the specificity appears to be low.…”

Section: Indiscriminant Binding Of Flavivirus Capsid To Nucleic Acidsmentioning

confidence: 53%

“…This face consists primarily of basic amino acids, lysine (K) and arginine (R). As shown by others, capsid appears to indiscriminately bind a range of nucleic acids in vitro including either single or double stranded RNA or DNA, suggesting non-specific interactions with the phosphate backbone [15,48,49]. However, the N-terminal domain of flavivirus capsids, unresolvable by crystallography, is flexible and also highly positively charged.…”

Section: Structure Of Flavivirus Capsid and Its Role In Packagingmentioning

confidence: 84%

Understanding Flavivirus Capsid Protein Functions: The Tip of the Iceberg

Sotcheff

Routh

2020

Pathogens

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Flaviviruses are enveloped positive-sense single-stranded RNA arboviruses, infectious to humans and many other animals and are transmitted primarily via tick or mosquito vectors. Capsid is the primary structural protein to interact with viral genome within virus particles and is therefore necessary for efficient packaging. However, in cells, capsid interacts with many proteins and nucleic acids and we are only beginning to understand the broad range of functions of flaviviral capsids. It is known that capsid dimers interact with the membrane of lipid droplets, aiding in both viral packaging and storage of capsid prior to packaging. However, capsid dimers can bind a range of nucleic acid templates in vitro, and likely interact with a range of targets during the flavivirus lifecycle. Capsid may interact with host RNAs, resulting in altered RNA splicing and RNA transcription. Capsid may also bind short interfering-RNAs and has been proposed to sequester these species to protect flaviviruses from the invertebrate siRNA pathways. Capsid can also be found in the nucleolus, where it wreaks havoc on ribosome biogenesis. Here we review flavivirus capsid structure, nucleic acid interactions and how these give rise to multiple functions. We also discuss how these features might be exploited either in the design of effective antivirals or novel vaccine strategies.

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Structure-guided paradigm shifts in flavivirus assembly and maturation mechanisms

Nicholls

Sevvana

Kühn

2020

Advances in Virus Research

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The flavivirus genus encompasses more than 75 unique viruses, including dengue virus which accounts for almost 390 million global infections annually. Flavivirus infection can result in a myriad of symptoms ranging from mild rash and flu-like symptoms, to severe encephalitis and even hemorrhagic fever. Efforts to combat the impact of these viruses have been hindered due to limited antiviral drug and vaccine development. However, the advancement of knowledge in the structural biology of flaviviruses over the last 25 years has produced unique perspectives for the identification of potential therapeutic targets. With particular emphasis on the assembly and maturation stages of the flavivirus life cycle, it is the goal of this review to comparatively analyze the structural similarities between flaviviruses to provide avenues for new research and innovation.

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Structural insight into the Zika virus capsid encapsulating the viral genome

Cited by 25 publications

References 12 publications

Capsid protein structure in Zika virus reveals the flavivirus assembly process

Capsid protein structure in Zika virus reveals the flavivirus assembly process

Understanding Flavivirus Capsid Protein Functions: The Tip of the Iceberg

Structure-guided paradigm shifts in flavivirus assembly and maturation mechanisms

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