Antibody-dependent enhancement (ADE) of dengue virus: Identification of the key amino acid that is vital in DENV vaccine research.

The Journal of Gene Medicine
Guohui CuiLifang Jiang

Abstract

The antibody-dependent enhancement (ADE) of dengue virus (DENV) has critically restricted vaccine development. Prior research suggested pr4 as the probable ADE epitope of DENV. Chimeric DENV was constructed by replacing the DENV pr4 gene with the corresponding Japanese encephalitis virus (JEV) gene to determine whether it can reduce ADE activities. An alanine scanning method and bioinformatics analysis were utilized to identify the amino acid of pr4 that was crucial as an ADE epitope. Chimeric virus reduced ADE and virulence. The amino acids at the following locations on the mutant peptides showed significantly reduced binding ability to prM antibody: pr4.5 (position 5 - leucine), pr4.6 (position 6 - leucine), pr4.7 (position 7 - phenyalanine) and pr4.16 (position 16 - cysteine). The four amino acids had formed a pocket-like structure, which could increase the possibility of binding to an antibody. ADE activities could be reduced by replacing the DENV pr4 gene with the corresponding JEV gene. Leucine at position 5, leucine at position 6, phenyalanine at position 7 and cysteine at position 16 were the key amino acid sites in the ADE response of DENV. The occurrence of ADE can potentially be reduced by the replacement of key amin...Continue Reading

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Citations

Oct 12, 2021·International Journal of Immunopathology and Pharmacology·Gabriela Athziri Sánchez-ZunoJosé Francisco Muñoz-Valle

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Methods Mentioned

BETA
PCR
in vitro transcription
transfection
flow cytometry
ELISA

Software Mentioned

BLAST
Swiss
Meg Align Compare
Prism
GraphPad
Pdb Viewer
Model

Related Concepts

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Antibody-Dependent Enhancement

Antibody-dependent enhancement of viral infection is the entry of virus into host cells mediated by antiviral antibodies interacting with Fc or complement receptors. This has been most extensively observed with the dengue virus. Find the latest research on antibody-dependent enhancement here.