Publications des scientifiques de l'IRD

Pompon Julien, Manuel M., Ng G. K., Wong B., Shan C., Manokaran G., Soto-Acosta R., Bradrick S. S., Ooi E. E., Missé Dorothée, 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), p. e1006535 [27 p.]. ISSN 1553-7366.

Titre du document
Dengue subgenomic flaviviral RNA disrupts immunity in mosquito salivary glands to increase virus transmission
Année de publication
2017
Type de document
Article référencé dans le Web of Science WOS:000406623700056
Auteurs
Pompon Julien, Manuel M., Ng G. K., Wong B., Shan C., Manokaran G., Soto-Acosta R., Bradrick S. S., Ooi E. E., Missé Dorothée, Shi P. Y., Garcia-Blanco M. A.
Source
PLOS Pathogens, 2017, 13 (7), p. e1006535 [27 p.] ISSN 1553-7366
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.
Plan de classement
Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010070861]
Identifiant IRD
fdi:010070861
Contact