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. 2010 Oct 5;5(10):e13149.
doi: 10.1371/journal.pone.0013149.

Differential protein modulation in midguts of Aedes aegypti infected with chikungunya and dengue 2 viruses

Stéphane Tchankouo-Nguetcheu  1 , Huot Khun, Laurence Pincet, Pascal Roux, Muriel Bahut, Michel Huerre, Catherine Guette, Valérie Choumet
Affiliations

Differential protein modulation in midguts of Aedes aegypti infected with chikungunya and dengue 2 viruses

Stéphane Tchankouo-Nguetcheu et al. PLoS One. .

Abstract

Background: Arthropod borne virus infections cause several emerging and resurgent infectious diseases. Among the diseases caused by arboviruses, dengue and chikungunya are responsible for a high rate of severe human diseases worldwide. The midgut of mosquitoes is the first barrier for pathogen transmission and is a target organ where arboviruses must replicate prior to infecting other organs. A proteomic approach was undertaken to characterize the key virus/vector interactions and host protein modifications that happen in the midgut for viral transmission to eventually take place.

Methodology and principal findings: Using a proteomics differential approach with two-Dimensional Differential in-Gel Electrophoresis (2D-DIGE), we defined the protein modulations in the midgut of Aedes aegypti that were triggered seven days after an oral infection (7 DPI) with dengue 2 (DENV-2) and chikungunya (CHIKV) viruses. Gel profile comparisons showed that the level of 18 proteins was modulated by DENV-2 only and 12 proteins were modulated by CHIKV only. Twenty proteins were regulated by both viruses in either similar or different ways. Both viruses caused an increase of proteins involved in the generation of reactive oxygen species, energy production, and carbohydrate and lipid metabolism. Midgut infection by DENV-2 and CHIKV triggered an antioxidant response. CHIKV infection produced an increase of proteins involved in detoxification.

Conclusion/significance: Our study constitutes the first analysis of the protein response of Aedes aegypti's midgut infected with viruses belonging to different families. It shows that the differentially regulated proteins in response to viral infection include structural, redox, regulatory proteins, and enzymes for several metabolic pathways. Some of these proteins like antioxidant are probably involved in cell protection. On the other hand, we propose that the modulation of other proteins like transferrin, hsp60 and alpha glucosidase, may favour virus survival, replication and transmission, suggesting a subversion of the insect cell metabolism by the arboviruses.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Distribution within the midguts of Ae. aegypti after oral infection with CHIKV or DENV-2.
Ae. aegypti mosquitoes were dissected at 7 DPI and were assayed by IFA to detect CHIKV viral antigen (red) (A) or DENV-2 viral antigen (green) (B). Actin network was labelled using Alexafluor 488 (A) (green) or 633 (B) (magenta) phalloidin. The magnification was 25x.
Figure 2
Figure 2. Quantification of CHIKV and DENV-2 RNA by RT-qPCR in infected midguts.
The viral RNA copy number was measured for each virus at 2, 7, and 10 DPI.
Figure 3
Figure 3. Two-dimensional profile of non-infected Ae. aegypti midgut protein extract.
The proteins were stained with Cy3. The pI and molecular weight scales are indicated in the Figure.
Figure 4
Figure 4. 2D-DIGE synthetic gel of Ae. aegypti midgut extract modulated in the analysis control/CHIKV infected profiles.
Protein spots differentially expressed are indicated by number. The pI and molecular weight scales are indicated in the Figure.
Figure 5
Figure 5. 2D-DIGE synthetic gel of Ae. aegypti midgut extracts showing spots modulated after analysis of control/DENV-2 profiles.
Protein spots differentially expressed are indicated by number. The pI and molecular weight scales are indicated in the Figure.
See this image and copyright information in PMC

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