Expression of dengue virus NS3 protein inDrosophilaalters its susceptibility to infection

Abstract

We developed a Drosophila model in which the dengue virus NS3 protein is expressed in a tissue specific and inducible manner. Dengue virus NS3 is a multifunctional protein playing a major role during viral replication. Both protease and helicase domains of NS3 are interacting with human and insect host proteins including innate immune components of the host machinery. We characterized the NS3 transgenic flies showing that NS3 expression did not affect fly development. To further study the links between NS3 and the innate immune response, we challenge the flies with gram-positive and gram-negative bacteria. Interestingly, the Drosophila transgenic flies expressing NS3 were more susceptible to bacterial infections than control flies. However ubiquitous or immune-specific NS3 expression affected neither the life span nor the response to a non-infectious stress of the flies. In conclusion, we generated a new in vivo system to study the functional impact of DENV NS3 protein on the innate immune response.

Flavivirus Infection and Regulation of Host Immune and Tissue Homeostasis in Insects

“…This information points toward a relationship between ZIKV gene expression, JAK/STAT and Notch signaling activity which is necessary for Drosophila growth and development, and induction of pathological defects in the fly (Figure 1A). In a similar manner, expression of the DENV NS3 protein (which promotes virus replication) in Drosophila transgenic flies reduces their survival response to bacterial infection, but not to abiotic stress, indicating a link between DENV NS3 activity and antimicrobial immune capacity (51). Finally, a genome-wide RNAi screen in Drosophila cells has identified a large number of genes encoding cellular factors, many of which are able to restrict WNV infection.…”

Drosophila melanogaster as a model host to study arbovirus–vector interaction

“…The Drosophila model system has been explored to study a variety of human infections and diseases [12][13][14][15][16][17][18] . Furthermore, the utility of D. melanogaster as a host model system for understanding cellular interactions of various human pathogens has been well-established 8,[19][20][21][22][23][24][25][26][27][28] . However, D. 4 melanogaster underutilized in arbovirus studies and holds great potential in the understanding mechanisms involved in arbovirus pathogenesis.…”

Differential humoral and cellular immunity induced by vaccination using plasmid DNA and protein recombinant expressing the NS3 protein of dengue virus type 3

“…Both protease and helicase domains of NS3 are interacting with human and insect host proteins including innate immune components of the host machinery [5]. The NS3 is a conserved protein among the different dengue serotypes, which elicits a strong cellular immune response after viral infection in humans and animal models [6, 7].…”