Global Cross-Talk of Genes of the Mosquito Aedes aegypti in Response to Dengue Virus Infection

Abstract

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.

Dengue virus infection induces chromatin remodeling at locus AAEL006536 in the midgut of Aedes aegypti

“…Putative target genes of this pathway, which participate in the mosquito's anti-dengue defense, have been identified. 26 The presence of REL-type TFBS suggests that this gene is a target of the Imd and/or the Toll immunity pathways. 27 The finding of more than one class of immunity TF binding sites suggests that this cis-regulatory site may integrate signals that activate more than one innate immunity pathway.…”

Further evidences for the mode of action of the larvicidal m-pentadecadienyl-phenol isolated from Myracrodruon urundeuva seeds against Aedes aegypti

“…Apoptotic cascades have already been described in Ae. aegypti, especially in response to viral infection with dengue fever ethiological agent (Bryant et al, 2008), some of them even mediated by a homologue of human tp53 (Behura et al, 2011)-a protein whose activity is linked to cell cycle arrest and apoptosis. The human homologue Rad23 is a known antagonist of p53, targeting the protein toward a proteasome-mediated degradation (Maritsi et al, 2006).…”

Influence of mosquito genotype on transcriptional response to dengue virus infection

“…The pathway analysis was performed with the KEGG (Kyoto Encyclopedia of Genes and Genomes, Japan) pathways annotated from A. aegypti genes (www.kegg.jp). The hypergeometric tests of GO association differentially expressed genes were conducted with gene counts as described in Behura et al (2011).…”

“…However, the potential for differential response of these genes or pathways to DENV infection in refractory versus susceptible mosquito genotypes is unclear. In earlier studies, we employed microarrays to compare gene expression profiles in susceptible and refractory genotypes of A. aegypti and identified genes that are expressed in a highly networked manner to trigger a susceptible or refractory response to DENV infection (Behura et al 2011; Chauhan et al . 2012).…”