Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.ppat.1006535
Title: Dengue subgenomic flaviviral RNA disrupts immunity in mosquito salivary glands to increase virus transmission
Authors: Pompon 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.
Keywords: animal cell
Article
controlled study
dengue
down regulation
female
gene disruption
gene expression
immune response
infection rate
mosquito
next generation sequencing
nonhuman
Northern blotting
sequence analysis
virus isolation
virus titration
virus transmission
Aedes
animal
dengue
Dengue virus
genetics
human
immunology
insect vector
metabolism
physiology
salivary gland
transmission
virology
virus replication
virus RNA
Aedes
Animals
Dengue
Dengue Virus
Humans
Insect Vectors
RNA, Viral
Salivary Glands
Virus Replication
Issue Date: 2017
Publisher: Public Library of Science
Citation: Pompon 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
Abstract: Globally 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.
Source Title: PLoS Pathogens
URI: https://scholarbank.nus.edu.sg/handle/10635/165374
ISSN: 15537366
DOI: 10.1371/journal.ppat.1006535
Appears in Collections:Staff Publications
Elements

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_ppat_1006535.pdf6.6 MBAdobe PDF

OPEN

NoneView/Download

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.