Influence of mosquito genotype on transcriptional response to dengue virus infection.

The mosquito Aedes aegypti is the principal vector that transmits dengue virus (DENV) to humans. The primary factors that trigger a susceptible or refractory interaction of A. aegypti with DENV are not well understood. In this study, our aim is to characterize the influence of vector genotype on differential gene expression of susceptible vs. refractory A. aegypti strains to DENV infection. To accomplish that, we identified differential expression of a set of complementary DNAs (cDNAs; n = 9,504) of the D2S3 (susceptible) and Moyo-D (refractory) strains of A. aegypti to DENV serotype 2 (JAM1409) and compared these results to the differential expression of cDNAs in a different susceptible vector genotype (Moyo-S) relative to the same refractory genotype (Moyo-D) identified from our previous study. We observed that, although the number of differentially expressed transcripts (DETs) was similar in both the studies, about ~95% of the DETs were distinct between Moyo-D/D2S3 vs. Moyo-D/Moyo-S. This suggested that A. aegypti response, to infection of a given genotype of dengue, is largely dependent upon the vector genotype. However, we observed a set of common DETs among the vector strains that were associated with predicted functions such as endocytosis, regulation of autophagy, peroxisome, and lipid metabolism that may be relatively universal in conferring mosquito response to DENV infection.

Comparative expression profiles of midgut genes in dengue virus refractory and susceptible Aedes aegypti across critical period for virus infection.

BACKGROUND: Aedes aegypti is the primary mosquito vector for dengue virus (DENV) worldwide. Infectivity of dengue virus varies among natural populations of this mosquito. How A. aegypti responds to DENV infection relative to which genes and associated pathways contribute to its differential susceptibility as a vector is not well defined. METHODS/PRINCIPAL FINDINGS: Here, we used custom cDNA microarrays to identify groups of genes that were differentially expressed in midgut tissues between susceptible and refractory strains in a highly time specific manner. While genes involved in protein processing in the endoplasmic reticulum, mRNA surveillance, and the proteasome were significantly up-regulated in the susceptible strain, several metabolic processes including glycolysis, glycan biosynthesis and Wnt pathway were active in the refractory strain. In addition, several key signaling genes were expressed as common responsive genes in both susceptible and refractory mosquitoes that may be necessary for signal transduction to trigger the appropriate host response to the viral infection. These are coordinately expressed in the form of tight gene networks and expression clusters that may be necessary to differentially contribute to the progression of dengue infection between the two strains. CONCLUSIONS: Our data show that highly correlated differential expression of responsive genes throughout the post infection period in A. aegypti midgut tissues is necessary for a coordinated transcriptional response of the mosquito genes to host or defend the viral infection.

Global cross-talk of genes of the mosquito Aedes aegypti in response to dengue virus infection.

BACKGROUND: The 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 RESULTS: To 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. CONCLUSIONS: Our 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.

Breeding structure of Aedes aegypti populations in Mexico varies by region.

A population genetic analysis of Aedes aegypti was conducted among 38 collections from throughout coastal regions of Mexico. Multiple collections were made within 5 cities to examine local patterns of gene flow. Single-strand conformation polymorphism analysis was used to screen for variation in a 387-bp region of the Nicotinamide Adenine Dinucleotide Dehydrogenase subunit 4 mitochondrial gene (ND4) and 25 haplotypes were detected. Northeastern Mexico collections were genetically differentiated from and had lower genetic diversity than Yucatan and Pacific coastal collections. Yucatan and Pacific collections were genetically homogeneous. Regression analysis of geographic distances and F(ST) values indicated that collections were genetically isolated by distance in the Pacific and the Yucatan, but not among collections in the northeast. Free gene flow occurred among all collections within 130 km of one another in the northeast and within 180 km in the Yucatan. F(ST) values were never large among Pacific collections, suggesting extensive gene flow along the Pacific coast.