title: Intra-epidemic evolutionary dynamics of a Dengue virus type 1 population reveal mutant spectra that correlate with disease transmission.
abstract: Dengue virus (DENV) is currently the most prevalent mosquito-borne viral pathogen. DENVs naturally exist as highly heterogeneous populations. Even though the descriptions on DENV diversity are plentiful, only a few studies have narrated the dynamics of intra-epidemic virus diversity at a fine scale. Such accounts are important to decipher the reciprocal relationship between viral evolutionary dynamics and disease transmission that shape dengue epidemiology. In the current study, we present a micro-scale genetic analysis of a monophyletic lineage of DENV-1 genotype III (epidemic lineage) detected from November 2012 to May 2014. The lineage was involved in an unprecedented dengue epidemic in Singapore during 2013-2014. Our findings showed that the epidemic lineage was an ensemble of mutants (variants) originated from an initial mixed viral population. The composition of mutant spectrum was dynamic and positively correlated with case load. The close interaction between viral evolution and transmission intensity indicated that tracking genetic diversity through time is potentially a useful tool to infer DENV transmission dynamics and thereby, to assess the epidemic risk in a disease control perspective. Moreover, such information is salient to understand the viral basis of clinical outcome and immune response variations that is imperative to effective vaccine design.
authors.affiliation: Environmental Health Institute, National Environment Agency, 11, Biopolis Way, #06-05-08, Singapore 138667.
authors.forename: Hapuarachchige Chanditha
authors.initials: HC
authors.lastname: Hapuarachchi
authors.affiliation: Environmental Health Institute, National Environment Agency, 11, Biopolis Way, #06-05-08, Singapore 138667.
authors.forename: Carmen
authors.initials: C
authors.lastname: Koo
authors.affiliation: Environmental Health Institute, National Environment Agency, 11, Biopolis Way, #06-05-08, Singapore 138667.
authors.forename: Relus
authors.initials: R
authors.lastname: Kek
authors.affiliation: Environmental Health Institute, National Environment Agency, 11, Biopolis Way, #06-05-08, Singapore 138667.
authors.forename: Helen
authors.initials: H
authors.lastname: Xu
authors.affiliation: Environmental Health Institute, National Environment Agency, 11, Biopolis Way, #06-05-08, Singapore 138667.
authors.forename: Yee Ling
authors.initials: YL
authors.lastname: Lai
authors.affiliation: Environmental Health Institute, National Environment Agency, 11, Biopolis Way, #06-05-08, Singapore 138667.
authors.forename: Lilac
authors.initials: L
authors.lastname: Liu
authors.affiliation: Environmental Health Institute, National Environment Agency, 11, Biopolis Way, #06-05-08, Singapore 138667.
authors.forename: Suet Yheng
authors.initials: SY
authors.lastname: Kok
authors.affiliation: Environmental Health Institute, National Environment Agency, 11, Biopolis Way, #06-05-08, Singapore 138667.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street #07-01, Matrix Building, Singapore 138671.
authors.forename: Raphael Lee Tze
authors.initials: RL
authors.lastname: Chuen
authors.affiliation: School of Life Sciences and Chemical Technology, Ngee Ann Polytechnic, Block 83, #04-00, 535 Clementi Road, Singapore 599489.
authors.forename: Kim-Sung
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street #07-01, Matrix Building, Singapore 138671.|School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore 637551.|National Public Health Laboratory (NPHL), Ministry of Health (MOH), 3 Biopolis Drive, #05-14 to 16, Synapse, Singapore 138623.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Maurer-Stroh
authors.affiliation: Environmental Health Institute, National Environment Agency, 11, Biopolis Way, #06-05-08, Singapore 138667.|School of Biological Sciences (SBS), Nanyang Technological University (NTU), 60 Nanyang Drive, Singapore 637551.
authors.forename: Lee Ching
authors.initials: LC
authors.lastname: Ng
mesh_terms: D000940:Antigenic Variation; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D005075:Biological Evolution; D003715:Dengue / Q000635:transmission / Q000821:virology*; D003716:Dengue Virus / Q000502:physiology*; D058872:Epidemics; D019143:Evolution, Molecular; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics; D012306:Risk; D017422:Sequence Analysis, DNA
chemical_list: D000956:Antigens, Viral; D012367:RNA, Viral