Dataset Information

Response of the mosquito protein interaction network to dengue infection.

ABSTRACT:

Background

Two fifths of the world's population is at risk from dengue. The absence of effective drugs and vaccines leaves vector control as the primary intervention tool. Understanding dengue virus (DENV) host interactions is essential for the development of novel control strategies. The availability of genome sequences for both human and mosquito host greatly facilitates genome-wide studies of DENV-host interactions.

Results

We developed the first draft of the mosquito protein interaction network using a computational approach. The weighted network includes 4,214 Aedes aegypti proteins with 10,209 interactions, among which 3,500 proteins are connected into an interconnected scale-free network. We demonstrated the application of this network for the further annotation of mosquito proteins and dissection of pathway crosstalk. Using three datasets based on physical interaction assays, genome-wide RNA interference (RNAi) screens and microarray assays, we identified 714 putative DENV-associated mosquito proteins. An integrated analysis of these proteins in the network highlighted four regions consisting of highly interconnected proteins with closely related functions in each of replication/transcription/translation (RTT), immunity, transport and metabolism. Putative DENV-associated proteins were further selected for validation by RNAi-mediated gene silencing, and dengue viral titer in mosquito midguts was significantly reduced for five out of ten (50.0%) randomly selected genes.

Conclusions

Our results indicate the presence of common host requirements for DENV in mosquitoes and humans. We discuss the significance of our findings for pharmacological intervention and genetic modification of mosquitoes for blocking dengue transmission.

SUBMITTER: Guo X

PROVIDER: S-EPMC3091628 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Publications

Response of the mosquito protein interaction network to dengue infection.

Guo Xiang X Xu Yao Y Bian Guowu G Pike Andrew D AD Xie Yan Y Xi Zhiyong Z

BMC genomics 20100616

<h4>Background</h4>Two fifths of the world's population is at risk from dengue. The absence of effective drugs and vaccines leaves vector control as the primary intervention tool. Understanding dengue virus (DENV) host interactions is essential for the development of novel control strategies. The availability of genome sequences for both human and mosquito host greatly facilitates genome-wide studies of DENV-host interactions.<h4>Results</h4>We developed the first draft of the mosquito protein i ...[more]

PMID: 20553610

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Project description:BackgroundThe mosquito Aedes aegypti is the primary vector of dengue virus (DENV) infection in humans, and DENV is the most important arbovirus across most of the subtropics and tropics worldwide. The early time periods after infection with DENV define critical cellular processes that determine ultimate success or failure of the virus to establish infection in the mosquito.Methods and resultsTo identify genes involved in these processes, we performed genome-wide transcriptome profiling between susceptible and refractory A. aegypti strains at two critical early periods after challenging them with DENV. Genes that responded coordinately to DENV infection in the susceptible strain were largely clustered in one specific expression module, whereas in the refractory strain they were distributed in four distinct modules. The susceptible response module in the global transcriptional network showed significant biased representation with genes related to energy metabolism and DNA replication, whereas the refractory response modules showed biased representation across different metabolism pathway genes including cytochrome P450 and DDT [1,1,1-Trichloro-2,2-bis(4-chlorophenyl) ethane] degradation genes, and genes associated with cell growth and death. A common core set of coordinately expressed genes was observed in both the susceptible and refractory mosquitoes and included genes related to the Wnt (Wnt: wingless [wg] and integration 1 [int1] pathway), MAPK (Mitogen-activated protein kinase), mTOR (mammalian target of rapamycin) and JAK-STAT (Janus Kinase - Signal Transducer and Activator of Transcription) pathways.ConclusionsOur data revealed extensive transcriptional networks of mosquito genes that are expressed in modular manners in response to DENV infection, and indicated that successfully defending against viral infection requires more elaborate gene networks than hosting the virus. These likely play important roles in the global-cross talk among the mosquito host factors during the critical early DENV infection periods that trigger the appropriate host action in susceptible vs. refractory mosquitoes.

Project description:Aedes aegypti transmits one of the most significant mosquito-borne viruses, dengue virus (DENV). The absence of effective vaccines and clinical treatments and the emergence of insecticide resistance in A. aegypti necessitate novel vector control strategies. A new approach uses the endosymbiotic bacterium Wolbachia pipientis to reduce the spread of arboviruses. However, the Wolbachia-mediated antiviral mechanism is not well understood. To shed light on this mechanism, we investigated an unexplored aspect of Wolbachia-virus-mosquito interaction. We used RNA sequencing to examine the transcriptional response of Wolbachia to DENV infection in A. aegypti Aag2 cells transinfected with the wAlbB strain of Wolbachia. Our results suggest that genes encoding an endoribonuclease (RNase HI), a regulator of sigma 70-dependent gene transcription (6S RNA), essential cellular, transmembrane, and stress response functions and primary type I and IV secretion systems were upregulated, while a number of transport and binding proteins of Wolbachia, ribosome structure, and elongation factor-associated genes were downregulated due to DENV infection. Furthermore, bacterial retrotransposon, transposable, and phage-related elements were found among the up- and downregulated genes. We show that Wolbachia elicits a transcriptional response to virus infection and identify differentially expressed Wolbachia genes mostly at the early stages of virus infection. These findings highlight Wolbachia's ability to alter its gene expression in response to DENV infection of the host cell. IMPORTANCE Aedes aegypti is a vector of several pathogenic viruses, including dengue, Zika, chikungunya, and yellow fever viruses, which are of importance to human health. Wolbachia is an endosymbiotic bacterium currently used in transinfected mosquitoes to suppress replication and transmission of dengue viruses. However, the mechanism of Wolbachia-mediated virus inhibition is not fully understood. While several studies have shown mosquitoes' transcriptional responses to dengue virus infection, none have investigated these responses in Wolbachia, which may provide clues to the inhibition mechanism. Our results suggest changes in the expression of a number of functionally important Wolbachia genes upon dengue virus infection, including those involved in stress responses, providing insights into the endosymbiont's reaction to virus infection.

Dataset Information

Response of the mosquito protein interaction network to dengue infection.

Background

Results

Conclusions

Publications

Response of the mosquito protein interaction network to dengue infection.

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