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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.

Original publication

DOI

10.1093/infdis/jiv536

Type

Journal article

Journal

J Infect Dis

Publication Date

15/03/2016

Volume

213

Pages

975 - 984

Keywords

Cambodia, Vietnam, dengue virus, envelope protein, evolution, fitness, genotype, lineage, neutralizing antibodies, Amino Acid Substitution, Antibodies, Neutralizing, Antibodies, Viral, Biological Evolution, Cloning, Molecular, Dengue, Dengue Virus, Evolution, Molecular, Gene Expression Regulation, Viral, Humans, Phylogeny, Serotyping, Viral Envelope Proteins