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Title: Stereophysicochemical variability plots highlight conserved antigenic areas in Flaviviruses

Abstract

Background: Flaviviruses, which include Dengue (DV) and West Nile (WN), mutate in response to immune system pressure. Identifying escape mutants, variant progeny that replicate in the presence of neutralizing antibodies, is a common way to identify functionally important residues of viral proteins. However, the mutations typically occur at variable positions on the viral surface that are not essential for viral replication. Methods are needed to determine the true targets of the neutralizing antibodies. Results: Stereophysicochemical variability plots (SVPs), 3-D images of protein structures colored according to variability, as determined by our PCPMer program, were used to visualize residues conserved in their physical chemical properties (PCPs) near escape mutant positions. The analysis showed 1) that escape mutations in the flavivirus envelope protein are variable residues by our criteria and 2) two escape mutants found at the same position in many flaviviruses sit above clusters of conserved residues from different regions of the linear sequence. Conservation patterns in Tcell epitopes in the NS3- protease suggest a similar mechanism of immune system evasion. Conclusion: The SVPs add another dimension to structurally defining the binding sites of neutralizing antibodies. They provide a useful aid for determining antigenically important regions and designing vaccines.

Authors:
 [1];  [2];  [3]
+ Show Author Affiliations
  1. Univ. of Texas Medical Branch at Galveston, TX (United States). Sealy Center for Structural Biology. Dept. of Human Biology, Chemistry and Genetics; Univ. of Texas Medical Branch at Galveston, TX (United States). Dept. of Microbiology and Immunology
  2. Univ. of Texas Medical Branch at Galveston, TX (United States). Sealy Center for Structural Biology. Dept. of Human Biology, Chemistry and Genetics
  3. Univ. of Texas Medical Branch at Galveston, TX (United States). Sealy Center for Structural Biology. Dept. of Human Biology, Chemistry and Genetics; Univ. of Texas Medical Branch at Galveston, TX (United States). Sealy Center for Vaccine Development. Dept. of Human Biology, Chemistry and Genetics
Publication Date:
Research Org.:
Univ. of Texas, Austin, TX (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
OSTI Identifier:
1626616
Grant/Contract Number:  
FG03-00ER63041
Resource Type:
Accepted Manuscript
Journal Name:
Virology Journal
Additional Journal Information:
Journal Volume: 2; Journal Issue: 1; Journal ID: ISSN 1743-422X
Publisher:
BioMed Central
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Virology

Citation Formats

Schein, Catherine H., Zhou, Bin, and Braun, Werner. Stereophysicochemical variability plots highlight conserved antigenic areas in Flaviviruses. United States: N. p., 2005. Web. doi:10.1186/1743-422x-2-40.
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Schein, Catherine H., Zhou, Bin, & Braun, Werner. Stereophysicochemical variability plots highlight conserved antigenic areas in Flaviviruses. United States. https://doi.org/10.1186/1743-422x-2-40
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Schein, Catherine H., Zhou, Bin, and Braun, Werner. Sat . "Stereophysicochemical variability plots highlight conserved antigenic areas in Flaviviruses". United States. https://doi.org/10.1186/1743-422x-2-40. https://www.osti.gov/servlets/purl/1626616.
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@article{osti_1626616,
title = {Stereophysicochemical variability plots highlight conserved antigenic areas in Flaviviruses},
author = {Schein, Catherine H. and Zhou, Bin and Braun, Werner},
abstractNote = {Background: Flaviviruses, which include Dengue (DV) and West Nile (WN), mutate in response to immune system pressure. Identifying escape mutants, variant progeny that replicate in the presence of neutralizing antibodies, is a common way to identify functionally important residues of viral proteins. However, the mutations typically occur at variable positions on the viral surface that are not essential for viral replication. Methods are needed to determine the true targets of the neutralizing antibodies. Results: Stereophysicochemical variability plots (SVPs), 3-D images of protein structures colored according to variability, as determined by our PCPMer program, were used to visualize residues conserved in their physical chemical properties (PCPs) near escape mutant positions. The analysis showed 1) that escape mutations in the flavivirus envelope protein are variable residues by our criteria and 2) two escape mutants found at the same position in many flaviviruses sit above clusters of conserved residues from different regions of the linear sequence. Conservation patterns in Tcell epitopes in the NS3- protease suggest a similar mechanism of immune system evasion. Conclusion: The SVPs add another dimension to structurally defining the binding sites of neutralizing antibodies. They provide a useful aid for determining antigenically important regions and designing vaccines.},
doi = {10.1186/1743-422x-2-40},
journal = {Virology Journal},
number = 1,
volume = 2,
place = {United States},
year = {Sat Jan 01 00:00:00 EST 2005},
month = {Sat Jan 01 00:00:00 EST 2005}
}
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https://doi.org/10.1186/1743-422x-2-40
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