Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pntd.0004052
Title: Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission
Authors: Sim S.
Aw P.P.K.
Wilm A.
Teoh G.
Hue K.D.T.
Nguyen N.M.
Nagarajan N. 
Simmons C.P.
Hibberd M.L. 
Keywords: abdomen
Aedes aegypti
Article
dengue
Dengue virus
Dengue virus 2
gene mapping
gene sequence
genetic variability
haplotype
human
next generation sequencing
nonhuman
polymerase chain reaction
population size
salivary gland
single nucleotide polymorphism
virus replication
virus transmission
adult
Aedes
animal
classification
Dengue virus
female
gastrointestinal tract
genetic selection
genetic variation
genetics
high throughput sequencing
isolation and purification
male
virology
young adult
NS1 protein, Dengue virus type 2
viral protein
virus RNA
Adult
Aedes
Animals
Dengue
Dengue Virus
Female
Gastrointestinal Tract
Genetic Variation
High-Throughput Nucleotide Sequencing
Humans
Male
Polymorphism, Single Nucleotide
RNA, Viral
Salivary Glands
Selection, Genetic
Viral Nonstructural Proteins
Young Adult
Issue Date: 2015
Citation: Sim S., Aw P.P.K., Wilm A., Teoh G., Hue K.D.T., Nguyen N.M., Nagarajan N., Simmons C.P., Hibberd M.L. (2015). Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission. PLoS Neglected Tropical Diseases 9 (9) : e0004052. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pntd.0004052
Abstract: Dengue virus (DENV) infection of an individual human or mosquito host produces a dynamic population of closely-related sequences. This intra-host genetic diversity is thought to offer an advantage for arboviruses to adapt as they cycle between two very different host species, but it remains poorly characterized. To track changes in viral intra-host genetic diversity during horizontal transmission, we infected Aedes aegypti mosquitoes by allowing them to feed on DENV2-infected patients. We then performed whole-genome deep-sequencing of human- and matched mosquito-derived DENV samples on the Illumina platform and used a sensitive variant-caller to detect single nucleotide variants (SNVs) within each sample. >90% of SNVs were lost upon transition from human to mosquito, as well as from mosquito abdomen to salivary glands. Levels of viral diversity were maintained, however, by the regeneration of new SNVs at each stage of transmission. We further show that SNVs maintained across transmission stages were transmitted as a unit of two at maximum, suggesting the presence of numerous variant genomes carrying only one or two SNVs each. We also present evidence for differences in selection pressures between human and mosquito hosts, particularly on the structural and NS1 genes. This analysis provides insights into how population drops during transmission shape RNA virus genetic diversity, has direct implications for virus evolution, and illustrates the value of high-coverage, whole-genome next-generation sequencing for understanding viral intra-host genetic diversity. ? 2015 Sim et al.
Source Title: PLoS Neglected Tropical Diseases
URI: https://scholarbank.nus.edu.sg/handle/10635/161929
ISSN: 19352727
DOI: 10.1371/journal.pntd.0004052
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