title: Evolutionarily Successful Asian 1 Dengue Virus 2 Lineages Contain One Substitution in Envelope That Increases Sensitivity to Polyclonal Antibody Neutralization.
abstract: 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.
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley.
authors.forename: Chunling
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley Department of Zoology, Center for Pathogen Evolution, University of Cambridge.
authors.forename: Leah C
authors.initials: LC
authors.lastname: Katzelnick
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley.
authors.forename: Magelda
authors.initials: M
authors.lastname: Montoya
authors.affiliation: Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, United Kingdom Oxford University Clinical Research Unit, Center for Tropical Medicine, Ho Chi Minh City, Vietnam.
authors.forename: Kien Duong Thi
authors.initials: KD
authors.lastname: Hue
authors.affiliation: Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, United Kingdom Oxford University Clinical Research Unit, Center for Tropical Medicine, Ho Chi Minh City, Vietnam Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute, Australia.
authors.forename: Cameron P
authors.initials: CP
authors.lastname: Simmons
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley.
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
mesh_terms: D019943:Amino Acid Substitution; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D005075:Biological Evolution; D003001:Cloning, Molecular; D003715:Dengue / Q000097:blood / Q000276:immunology / Q000821:virology; D003716:Dengue Virus / Q000145:classification* / Q000235:genetics*; D019143:Evolution, Molecular; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006801:Humans; D010802:Phylogeny; D012703:Serotyping; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014759:Viral Envelope Proteins
keywords: Cambodia; Vietnam; dengue virus; envelope protein; evolution; fitness; genotype; lineage; neutralizing antibodies