Evolutionarily Successful Asian 1 Dengue Virus 2 Lineages Contain One Substitution in Envelope That Increases Sensitivity to Polyclonal Antibody Neutralization
Katzelnick, Leah C.
Hue, Kien Duong Thi
Simmons, Cameron P.
Journal of Infectious Diseases
Oxford University Press
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Wang, C., Katzelnick, L. C., Montoya, M., Hue, K. D. T., Simmons, C. P., & Harris, E. (2015). Evolutionarily Successful Asian 1 Dengue Virus 2 Lineages Contain One Substitution in Envelope That Increases Sensitivity to Polyclonal Antibody Neutralization. Journal of Infectious Diseases, 213 (6), 975-984. https://doi.org/10.1093/infdis/jiv536
This is the author accepted manuscript. The final version is available from Oxford University Press via http://dx.doi.org/10.1093/infdis/jiv536
The 4 dengue virus serotypes (DENV-1–4) cause the most prevalent mosquito-borne viral disease of humans worldwide. DENV-2 Asian 1 (A1) genotype viruses replaced the Asian-American (AA) genotype in Vietnam and Cambodia, after which A1 viruses containing Q or M at envelope (E) residue 160 became more prevalent than those with residue 160K in both countries (2008–2011). We investigated whether these substitutions conferred a fitness advantage by measuring neutralizing antibody titer against reporter virus particles (RVPs) representing AA, A1-160K, A1-160Q, and A1-160M, using patient sera from Vietnam and a well-characterized Nicaraguan cohort. Surprisingly, we found that A1-160Q and A1-160M RVPs were better neutralized by heterologous antisera than A1-160K. Despite this, Vietnamese patients infected with A1-160Q or A1-160M viruses had higher viremia levels than those infected with A1-160K. We thus found that independent lineages in Vietnam and Cambodia acquired a substitution in E that significantly increased polyclonal neutralization but nonetheless were successful in disseminating and infecting human hosts.
dengue virus, neutralizing antibodies, envelope protein, fitness, evolution, genotype, lineage, Vietnam, Cambodia
This work was supported by the Bill and Melinda Gates Foundation and the Instituto Carlos Slim de la Salud (FIRST Program); the Nicaraguan Pediatric Dengue Cohort Study was supported by the Pediatric Dengue Vaccine Initiative (grant VE-1 to E. H.) and the National Institutes of Health (NIH) R01 AI099631 (to Dr Angel Balmaseda); and L. C. K. was supported by a Gates Cambridge Scholarship and the NIH Oxford-Cambridge Scholars Program.
External DOI: https://doi.org/10.1093/infdis/jiv536
This record's URL: https://www.repository.cam.ac.uk/handle/1810/253721