Dengue viruses cluster antigenically but not as discrete serotypes

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Dengue viruses cluster antigenically but not as discrete serotypes by Leah C. Katzelnick, Judith M. Fonville, Gregory D. Gromowski, Jose Bustos Arriaga, Angela Green, Sarah L. James, Louis Lau, Magelda Montoya, Chunling Wang, Laura A. VanBlargan, Colin A. Russell, Hlaing Myat Thu, Theodore C. Pierson, Philippe Buchy, John G. Aaskov, Jorge L. Muñoz-Jordán, Nikos Vasilakis, Robert V. Gibbons, Robert B. Tesh, Albert D.M.E. Osterhaus, Ron A.M. Fouchier, Anna Durbin, Cameron P. Simmons, Edward C. Holmes, Eva Harris, Stephen S. Whitehead, and Derek J. Smith Science Volume 349(6254):1338-1343 September 18, 2015 Published by AAAS

Fig. 1 Genetic analyses of the DENV panel (n = 47). Genetic analyses of the DENV panel (n = 47). (A) Phylogenetic tree showing the evolutionary relationships of DENV E gene sequences. Sequences were aligned with MAFFT, and a maximum likelihood tree was estimated using a general time-reversible model, accounting for both among-site rate variation and invariant sites (GTR+Γ4+I). Bootstrap support values of at least 75% are shown. (B) Amino acid map of DENV E protein sequences (493 to 495 amino acids in length). The total amino acid differences between pairs of E sequences correspond to distances between points on the geometric display. Leah C. Katzelnick et al. Science 2015;349:1338-1343 Published by AAAS

Fig. 2 Antigenic map of the DENV panel (n = 46) titrated against African green monkey antisera drawn 3 months after infection (n = 36). Antigenic map of the DENV panel (n = 46) titrated against African green monkey antisera drawn 3 months after infection (n = 36). Each unit of antigenic distance (length of one grid-square side, measured in any direction) is equivalent to a twofold dilution in the neutralization assay. Each antiserum (open shape) and virus (closed shape) is colored according to the infecting genetic type (16). The size and shape of each point represent the confidence area of its position. Leah C. Katzelnick et al. Science 2015;349:1338-1343 Published by AAAS

Fig. 3 Human primary infection antigenic maps. Human primary infection antigenic maps. (A) Antisera from individuals inoculated with each monovalent component of the NIH live vaccine (10 per group) were drawn 42 days after infection and titrated against 36 viruses in the DENV panel. (B) Antisera from 20 Nicaraguan children drawn in the year after their first DENV infections were titrated against an antigenically diverse subset of the DENV panel (n = 14). Leah C. Katzelnick et al. Science 2015;349:1338-1343 Published by AAAS

Fig. 4 Antigenic maps of the DENV panel made with antisera drawn from NHPs 1 and 5 months after infection. Antigenic maps of the DENV panel made with antisera drawn from NHPs 1 and 5 months after infection. (A) An antigenic map of 47 DENV isolates titrated against 36 NHP antisera drawn 1 month after infection. Colored arrows (DENV1, yellow; DENV2, blue; DENV3, green; DENV4, red) show the change in antiserum positions between 1 and 3 months. The black arrows show the average shift in serum position for each DENV type. The star denotes the antigenic center for each DENV type. (B) An antigenic map of 37 DENV isolates titrated against 16 NHP antisera drawn 5 months after infection. Arrows point from positions of antisera at 3 months to the corresponding 5-month positions. Leah C. Katzelnick et al. Science 2015;349:1338-1343 Published by AAAS