Tracking Dengue Virus Intra-host Genetic Diversity during Human-to-Mosquito Transmission

PLoS Neglected Tropical Diseases
Shuzhen SimMartin L Hibberd

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, parti...Continue Reading

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Mar 5, 2016·Genome Biology·Shuzhen Sim, Martin L Hibberd
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Methods Mentioned

BETA
Illumina sequencing
PCR

Software Mentioned

LoFreq
Viral Pipeline Runner ( ViPR Aligner
CASAVA

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