Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1006535
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dc.titleDengue subgenomic flaviviral RNA disrupts immunity in mosquito salivary glands to increase virus transmission
dc.contributor.authorPompon J.
dc.contributor.authorManuel M.
dc.contributor.authorNg G.K.
dc.contributor.authorWong B.
dc.contributor.authorShan C.
dc.contributor.authorManokaran G.
dc.contributor.authorSoto-Acosta R.
dc.contributor.authorBradrick S.S.
dc.contributor.authorOoi E.E.
dc.contributor.authorMissé D.
dc.contributor.authorShi P.-Y.
dc.contributor.authorGarcia-Blanco M.A.
dc.date.accessioned2020-03-13T05:22:19Z
dc.date.available2020-03-13T05:22:19Z
dc.date.issued2017
dc.identifier.citationPompon J., Manuel M., Ng G.K., Wong B., Shan C., Manokaran G., Soto-Acosta R., Bradrick S.S., Ooi E.E., Missé D., Shi P.-Y., Garcia-Blanco M.A. (2017). Dengue subgenomic flaviviral RNA disrupts immunity in mosquito salivary glands to increase virus transmission. PLoS Pathogens 13 (7) : e1006535. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.ppat.1006535
dc.identifier.issn15537366
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/165374
dc.description.abstractGlobally re-emerging dengue viruses are transmitted from human-to-human by Aedes mosquitoes. While viral determinants of human pathogenicity have been defined, there is a lack of knowledge of how dengue viruses influence mosquito transmission. Identification of viral determinants of transmission can help identify isolates with high epidemiological potential. Additionally, mechanistic understanding of transmission will lead to better understanding of how dengue viruses harness evolution to cycle between the two hosts. Here, we identified viral determinants of transmission and characterized mechanisms that enhance production of infectious saliva by inhibiting immunity specifically in salivary glands. Combining oral infection of Aedes aegypti mosquitoes and reverse genetics, we identified two 3’ UTR substitutions in epidemic isolates that increased subgenomic flaviviral RNA (sfRNA) quantity, infectious particles in salivary glands and infection rate of saliva, which represents a measure of transmission. We also demonstrated that various 3’UTR modifications similarly affect sfRNA quantity in both whole mosquitoes and human cells, suggesting a shared determinism of sfRNA quantity. Furthermore, higher relative quantity of sfRNA in salivary glands compared to midgut and carcass pointed to sfRNA function in salivary glands. We showed that the Toll innate immune response was preferentially inhibited in salivary glands by viruses with the 3’UTR substitutions associated to high epidemiological fitness and high sfRNA quantity, pointing to a mechanism for higher saliva infection rate. By determining that sfRNA is an immune suppressor in a tissue relevant to mosquito transmission, we propose that 3’UTR/sfRNA sequence evolution shapes dengue epidemiology not only by influencing human pathogenicity but also by increasing mosquito transmission, thereby revealing a viral determinant of epidemiological fitness that is shared between the two hosts. © 2017 Pompon et al.
dc.publisherPublic Library of Science
dc.sourceUnpaywall 20200320
dc.subjectanimal cell
dc.subjectArticle
dc.subjectcontrolled study
dc.subjectdengue
dc.subjectdown regulation
dc.subjectfemale
dc.subjectgene disruption
dc.subjectgene expression
dc.subjectimmune response
dc.subjectinfection rate
dc.subjectmosquito
dc.subjectnext generation sequencing
dc.subjectnonhuman
dc.subjectNorthern blotting
dc.subjectsequence analysis
dc.subjectvirus isolation
dc.subjectvirus titration
dc.subjectvirus transmission
dc.subjectAedes
dc.subjectanimal
dc.subjectdengue
dc.subjectDengue virus
dc.subjectgenetics
dc.subjecthuman
dc.subjectimmunology
dc.subjectinsect vector
dc.subjectmetabolism
dc.subjectphysiology
dc.subjectsalivary gland
dc.subjecttransmission
dc.subjectvirology
dc.subjectvirus replication
dc.subjectvirus RNA
dc.subjectAedes
dc.subjectAnimals
dc.subjectDengue
dc.subjectDengue Virus
dc.subjectHumans
dc.subjectInsect Vectors
dc.subjectRNA, Viral
dc.subjectSalivary Glands
dc.subjectVirus Replication
dc.typeArticle
dc.contributor.departmentDEAN'S OFFICE (DUKE-NUS MEDICAL SCHOOL)
dc.contributor.departmentMICROBIOLOGY AND IMMUNOLOGY
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.doi10.1371/journal.ppat.1006535
dc.description.sourcetitlePLoS Pathogens
dc.description.volume13
dc.description.issue7
dc.description.pagee1006535
dc.published.statePublished
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