The role of capsid in the flaviviral life cycle and perspectives for vaccine development

He, Ying; Wang, Mingshu; Chen, Shun; Cheng, Anchun

doi:10.1016/j.vaccine.2020.08.053

Cited by 9 publications

(13 citation statements)

References 98 publications

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“…Previous studies have shown that CP plays multiple roles in the flaviviral life cycle. Its major function is the formation of the NC core, which participates in the viral assembly process, but it is also involved in vRNA replication via conserved RNA secondary structures in the N-terminus of the capsid gene ( 12 ). Therefore, first, the RNA secondary structure of the CQW1 capsid gene was predicted via homologous modelling using RNAstructure 6.0.1.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, first, the RNA secondary structure of the CQW1 capsid gene was predicted via homologous modelling using RNAstructure 6.0.1. In this model ( Figure 1A ), the first 100 nucleotides of the capsid gene are involved in the formation of SLB, 5’DAR and 5’CS, cHP and DCS-PK, and all of these cis-elements are conserved in the Flavivirus genus and are significant for vRNA replication ( 12 ).…”

Section: Resultsmentioning

confidence: 99%

“…The in vitro growth properties of ΔC20-43 and ΔC64-96 in BHK-21 cells showed that ΔC20-43 was more attenuated than ΔC64-96 compared with WT. Although the flexible N-terminus and α1 are supposed to help CP to adopt different conformations for various physiological processes ( 12 ), the results of the packaging assay indicate that the C-prM protein with ΔC20-43 deletion has little effect on its ability to package the replicon RNA; in comparison, Δ64-96 deletion severely impairs its packaging efficiency, and it would result in secretion of non-infectious SVPs in the expense of virions ( 15 ). Besides, the results revealed by the replicon assay indicate that ΔC20-43 deletion also attenuated vRNA replication, on account of the DCS-PK element was removed in ΔC20-43 mutant ( Figure 1C ).…”

Section: Discussionmentioning

confidence: 99%

“…Positively charged a4 is proposed as a vRNA-binding site; in addition, a4-a4' is critical for preserving the overall stability of CP dimer formation, and an unstable a4-a4' helix pair would result in the formation of the dimer being prevented (10). Furthermore, the flexible N-terminus and a1helix may regulate the conformation exchange of CP for various physiological processes (12). Dysfunction of CP results in the production of subviral particles (SVPs) at the expense of infectious virions (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

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Replication/Assembly Defective Avian Flavivirus With Internal Deletions in the Capsid Can Be Used as an Approach for Living Attenuated Vaccine

Wang

Guo

et al. 2021

Front. Immunol.

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Avian Tembusu virus (TMUV) is a novel flavivirus causing severe egg drop and fatal encephalitis in avian in Asia. In the present study, we screened the structural and functional requirements of TMUV capsid protein (CP) for viral morphogenesis using reverse genetics methods in combination with replicon packaging assays. TMUV-CP showed dramatic functional and structural flexibility, and even though 44 residues were removed from the N-terminus, it was still capable of packaging replicon RNA; in addition, 33 residues were deleted from the C-terminus (containing nearly the entire α4-helix), and infectious particles were still produced, although α4-α4’ is supposedly vital for CP dimerization and nucleocapsid formation. We further analyzed two mutants (ΔC20-43 and ΔC64-96 viruses) with relatively large deletions that still replicated well in BHK-21 cells. Our data indicate that internal deletions within CP impaired viral replication or assembly, resulting in attenuated virus proliferation in cells and attenuated virulence in duck embryos, and these deletion mutations are quite stable in cell culture. An in vivo assay indicated that both ΔC20-43 virus and ΔC64-96 virus were highly attenuated in ducklings but still immunogenic. Single-dose immunization with ΔC20-43 virus or ΔC64-96 virus could protect ducklings from a lethal challenge with good antigen clearance. Together, our data shed light on replication/assembly defective TMUV with internal deletions in CP and provide an effective approach to attenuate viral virulence in live vaccines without changing the antigen composition.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Replication/Assembly Defective Avian Flavivirus With Internal Deletions in the Capsid Can Be Used as an Approach for Living Attenuated Vaccine

Wang

Guo

et al. 2021

Front. Immunol.

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“…DEN-2 serotype also binds with HSP70/ HSP90, GRP78, and CD14-associated protein. Both the DEN 1-3 serotypes bind to Laminin receptor bind [12,13].…”

Section: Introductionmentioning

confidence: 99%

Heparan Sulfate: Landing Site for the Dengue Viral Strains to Gain Entry to the Host Cells

Papulzai¹,

John²,

Malla³

2021

Asian J Pharm Clin Res

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Humans usually contract dengue by being bitten by arthropods, and more than 3.6 billion people are at risk per year. Although studies are conducted to screen and trace out the possible pathophysiology of the virus, an adequate receptor-based study has not been completed. Understanding how the dengue virus (DV) engraves its landing sites requires identification of such cellular receptors. In many model studies, heparan sulfate (HS) has been reported to act as a DV receptor under various conditions. However, the physiological relevance of these findings remains uncertain. Therefore, it is still unclear whether HS is used by viral strains or not, and if at all used by clinical or non-cell culture-adapted strains of DV. The present review aims to identify relevant experimental evidences that confirm the possible interaction between envelope protein and HS chains. We collected data from a series of studies to conclude the interactive role.

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Development and characterization of an inducible assay system to measure Zika virus capsid interactions

Huang

Wang

et al. 2022

Journal of Medical Virology

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The global spread of the mosquito‐borne Zika virus (ZIKV) infection and its complications including Guillain‐Barré syndrome and fetus microcephaly in 2015 have made ZIKV as a significant public health threat. The capsid protein plays crucial roles in ZIKV replication and thus represents an attractive therapeutic target. However, inhibitors of ZIKV capsid assembly have not been rigorously identified due to the lack of a target‐based screening system. In this study, we developed a novel ZIKV capsid interaction method based on a split‐luciferase complementation assay, which can be used to measure and quantify ZIKV capsid–capsid (C–C) interaction by the restored luciferase signal when capsid proteins interact with each other. Furthermore, a Tet‐on inducible stable cell line was generated to screen inhibitors of capsid dimerization. By using of this system, peptides (Pep.15‐24 in the N‐terminal region of ZIKV capsid protein and Pep.44‐58 in the α2 helix of ZIKV capsid protein) were identified to inhibit ZIKV C–C interaction. Overall, this study developed a novel inducible assay system to measure ZIKV capsid interaction and identify ZIKV capsid multimerization inhibitors, which will be applied for future discovery of ZIKV assembly inhibitors.

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The role of capsid in the flaviviral life cycle and perspectives for vaccine development

Cited by 9 publications

References 98 publications

Replication/Assembly Defective Avian Flavivirus With Internal Deletions in the Capsid Can Be Used as an Approach for Living Attenuated Vaccine

Replication/Assembly Defective Avian Flavivirus With Internal Deletions in the Capsid Can Be Used as an Approach for Living Attenuated Vaccine

Heparan Sulfate: Landing Site for the Dengue Viral Strains to Gain Entry to the Host Cells

Development and characterization of an inducible assay system to measure Zika virus capsid interactions

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