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Title: Stereophysicochemical variability plots highlight conserved antigenic areas in Flaviviruses

Journal Article · · Virology Journal
 [1];  [2];  [3]
  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
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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.

Research Organization:
Univ. of Texas, Austin, TX (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
Grant/Contract Number:
FG03-00ER63041
OSTI ID:
1626616
Journal Information:
Virology Journal, Vol. 2, Issue 1; ISSN 1743-422X
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (4)

Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus journal December 2006
Dynamic Interaction of the Measles Virus Hemagglutinin with Its Receptor Signaling Lymphocytic Activation Molecule (SLAM, CD150) journal February 2008
AllerTOP v.2—a server for in silico prediction of allergens journal May 2014
An Approach for a Synthetic CTL Vaccine Design against Zika Flavivirus Using Class I and Class II Epitopes Identified by Computer Modeling journal June 2017

Figures / Tables (7)

Table 1(p. 2)table Table 1
Table 2(p. 2)table Table 2
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Figure 4(p. 6)figure Figure 4
Figure 5(p. 7)figure Figure 5

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