Stereophysicochemical variability plots highlight conserved antigenic areas in Flaviviruses

Catherine H. Schein, Bin Zhou, Werner Braun

Research output: Contribution to journalArticle

15 Citations (Scopus)

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 T-cell 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.

Original languageEnglish (US)
Article number40
JournalVirology Journal
Volume2
DOIs
StatePublished - Apr 21 2005

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Flavivirus
Neutralizing Antibodies
Immune System
Immune Evasion
Mutation
T-Lymphocyte Epitopes
Three-Dimensional Imaging
Dengue
Viral Proteins
Proteins
Peptide Hydrolases
Vaccines
Binding Sites
Pressure

ASJC Scopus subject areas

  • Virology
  • Genetics(clinical)

Cite this

Stereophysicochemical variability plots highlight conserved antigenic areas in Flaviviruses. / Schein, Catherine H.; Zhou, Bin; Braun, Werner.

In: Virology Journal, Vol. 2, 40, 21.04.2005.

Research output: Contribution to journalArticle

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