A Simple Method for the Design and Development of Flavivirus NS1 Recombinant Proteins Using an In Silico Approach

Park, Chulmin; Kim, Won-Bok; Cho, Sung‐Yeon; Oh, Eun‐Jee; Lee, Hyeyoung; Kang, Kyungjoon; Lee, Yoon-Suk; Lee, Dong Gun

doi:10.1155/2020/3865707

Cited by 5 publications

(8 citation statements)

References 37 publications

(41 reference statements)

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“…The UniprotKB accession numbers for aligned sequences are as follow: DENV-1, P27909; DENV-2, P29991; DENV-3, Q6YMS3; DENV-4, Q2YHF0; JEV, P27395; TBEV, Q01299; WNVm, P06935; YFV, Q6J3P1; and ZIKV, Q32ZE1. The conserved regions are indicated in red, whereas the non-conserved regions are in white . The conservation scale shown in yellow refers to the degree of similarity between amino acid or nucleotide residues at a particular position in a sequence across different members of a group or family of related sequences.…”

Section: Flavivirus Ns1 Proteinmentioning

confidence: 99%

“…The conserved regions are indicated in red, whereas the non-conserved regions are in white. 94 The conservation scale shown in yellow refers to the degree of similarity between amino acid or nucleotide residues at a particular position in a sequence across different members of a group or family of related sequences. polyprotein is directed to the ER because of the final 24 amino acids in the E protein, which functions as a signal sequence, translocating the NS1 protein into the ER lumen.…”

Section: ■ Flaviviral Life Cyclementioning

confidence: 99%

“…NS1-mediated disease pathogenesis as well as the protective effects from NS1 immunization have been demonstrated mostly using mouse models challenged with mouse-adapted DENV strains or mouse models that produce mild symptoms following an infection. A study done by Lee et al, 2020, revealed that the pathogenic role of NS1 protein may be dependent on the viral strain. 272 In this study, non-mouseadapted DENV-2 strains, D2Y98P and EHIE2862Y15, were used to induce virulency in ADE mouse models (A129 mice with defective type I IFN pathway and AG129 mice with defective type I and II IFN pathways) to determine if immunization with NS1 or anti-NS1 antibodies would confer protection against a lethal DENV challenge.…”

Section: Disease Pathogenesis May Be Strain-dependentmentioning

confidence: 99%

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Roles of NS1 Protein in Flavivirus Pathogenesis

Perera,

Ranadeva,

Sirisena

et al. 2023

ACS Infect. Dis.

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Flaviviruses such as dengue, Zika, and West Nile viruses are highly concerning pathogens that pose significant risks to public health. The NS1 protein is conserved among flaviviruses and is synthesized as a part of the flavivirus polyprotein. It plays a critical role in viral replication, disease progression, and immune evasion. Post-translational modifications influence NS1's stability, secretion, antigenicity, and interactions with host factors. NS1 protein forms extensive interactions with host cellular proteins allowing it to affect vital processes such as RNA processing, gene expression regulation, and cellular homeostasis, which in turn influence viral replication, disease pathogenesis, and immune responses. NS1 acts as an immune evasion factor by delaying complement-dependent lysis of infected cells and contributes to disease pathogenesis by inducing endothelial cell damage and vascular leakage and triggering autoimmune responses. Anti-NS1 antibodies have been shown to cross-react with host endothelial cells and platelets, causing autoimmune destruction that is hypothesized to contribute to disease pathogenesis. However, in contrast, immunization of animal models with the NS1 protein confers protection against lethal challenges from flaviviruses such as dengue and Zika viruses. Understanding the multifaceted roles of NS1 in flavivirus pathogenesis is crucial for effective disease management and control. Therefore, further research into NS1 biology, including its host protein interactions and additional roles in disease pathology, is imperative for the development of strategies and therapeutics to combat flavivirus infections successfully. This Review provides an in-depth exploration of the current available knowledge on the multifaceted roles of the NS1 protein in the pathogenesis of flaviviruses.

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Section: Flavivirus Ns1 Proteinmentioning

confidence: 99%

Section: ■ Flaviviral Life Cyclementioning

confidence: 99%

Section: Disease Pathogenesis May Be Strain-dependentmentioning

confidence: 99%

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Roles of NS1 Protein in Flavivirus Pathogenesis

Perera,

Ranadeva,

Sirisena

et al. 2023

ACS Infect. Dis.

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“…Recombinant NS5 was produced in HEK293T cells for phosphorylation characterization [ 73 , 74 ]. Recombinant YFV NS1 was obtained in E. coli strain Lemo21 (DE3) using vector pBT7-N-His [ 75 ]. NS1 and E proteins were also produced in insect and mammalian cells [ 76 ].…”

Section: Yellow Fever Virusmentioning

confidence: 99%

Anti-Flavivirus Vaccines: Review of the Present Situation and Perspectives of Subunit Vaccines Produced in Escherichia coli

et al. 2020

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This article aims to review the present status of anti-flavivirus subunit vaccines, both those at the experimental stage and those already available for clinical use. Aspects regarding development of vaccines to Yellow Fever virus, (YFV), Dengue virus (DENV), West Nile virus (WNV), Zika virus (ZIKV), and Japanese encephalitis virus (JEV) are highlighted, with particular emphasis on purified recombinant proteins generated in bacterial cells. Currently licensed anti-flavivirus vaccines are based on inactivated, attenuated, or virus-vector vaccines. However, technological advances in the generation of recombinant antigens with preserved structural and immunological determinants reveal new possibilities for the development of recombinant protein-based vaccine formulations for clinical testing. Furthermore, novel proposals for multi-epitope vaccines and the discovery of new adjuvants and delivery systems that enhance and/or modulate immune responses can pave the way for the development of successful subunit vaccines. Nonetheless, advances in this field require high investments that will probably not raise interest from private pharmaceutical companies and, therefore, will require support by international philanthropic organizations and governments of the countries more severely stricken by these viruses.

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“…Embora amplamente utilizado, o sorodiagnóstico pode ser problemático, devido a resultados falsos positivos com reatividade cruzada, enquanto outros Flavivírus se espalham juntos (HENRIQUE et al, 2020) [6]. Desse modo, é necessário desenvolver outras possibilidades para resolver esses problemas de reatividade cruzada (PARK et al, 2020) [2]. A interpretação de análises em larga escala depende de métodos comparativos e preditivos nos quais os bancos de dados biológicos desempenham um papel fundamental.…”

Section: Introductionunclassified