Infection with dengue-2 virus alters proteins in naturally expectorated saliva of Aedes aegypti mosquitoes

Abstract

BackgroundDengue virus (DENV) is responsible for up to approximately 300 million infections and an increasing number of deaths related to severe manifestations each year in affected countries throughout the tropics. It is critical to understand the drivers of this emergence, including the role of vector-virus interactions. When a DENV-infected Aedes aegypti mosquito bites a vertebrate, the virus is deposited along with a complex mixture of salivary proteins. However, the influence of a DENV infection upon the expectorated salivary proteome of its vector has yet to be determined.MethodsTherefore, we conducted a proteomic analysis using 2-D gel electrophoresis coupled with mass spectrometry based protein identification comparing the naturally expectorated saliva of Aedes aegypti infected with DENV-2 relative to that of uninfected Aedes aegypti.ResultsSeveral proteins were found to be differentially expressed in the saliva of DENV-2 infected mosquitoes, in particular proteins with anti-hemostatic and pain inhibitory functions were significantly reduced. Hypothetical consequences of these particular protein reductions include increased biting rates and transmission success, and lead to alteration of transmission potential as calculated in our vectorial capacity model.ConclusionsWe present our characterizations of these changes with regards to viral transmission and mosquito blood-feeding success. Further, we conclude that our proteomic analysis of Aedes aegypti saliva altered by DENV infection provides a unique opportunity to identify pro-viral impacts key to virus transmission.

Aedes aegypti salivary protein “aegyptin” co-inoculation modulates dengue virus infection in the vertebrate host

“…Analysis of expectorated saliva from DENV2 infected Ae. aegypti using 2D gel electrophoresis and LC-MS/MS has previously identified a subclade I aegyptin (gi|18568322) that was reduced 14.1-fold when compared to saliva from uninfected mosquitoes [34]. This aegyptin has also been referred to as “SAAG-4,” which has demonstrated the capacity to suppress IFN-γ expression while elevating IL-4 expression by CD4+ T cells outside the context of a viral infection [26].…”

“…Analogously, a reduction in expectorated aegyptin, as was observed in DENV infected Ae. aegypti mosquitoes, may result in greater viremia titers at this time point, which has been shown to lead to increased acquisition rates by mosquitoes from human clinical patients [34, 46]. The increase in DENV + aegyptin viremia titer seen on day 5 post inoculation (mean = 4.36 PFU*/mL) may not result in meaningful differences in transmission when compared to the DENV alone cohort (mean = 1.39 PFU*/mL) given the relatively minimal magnitude of these titers.…”

“…aegypti saliva has been shown to elicit specific IgG and IgE responses in humans [23, 32]. Recent studies have described the effect that DENV infection has on protein expression in the salivary glands or expectorated saliva and postulates how these changes could be relevant to virus transmission [33, 34]. Among the proteins that were found in lower abundance in Ae.…”

Impact of insect salivary proteins in blood feeding, host immunity, disease, and in the development of biomarkers for vector exposure

“…aegypti and Ae. albopictus [25,27,28], analysis of the actual saliva reveals reduced amounts of adenosine deaminase, aegyptin, and serpin [24]. Infection of Ae.…”

AeMOPE-1: um novo peptídeo imunomodulador salivar de <i>Aedes aegypti </i>com potencial terapêutico na colite experimental.

“…Alguns trabalhos demonstraram o aumento dos níveis séricos de anticorpos do tipo Th2 (IgE e IgG1) em camundongos expostos a sucessivas picadas, imunizados com alérgenos ou com EGS do mosquito (BARROS et al, 2016;SIMONS, , 2004 Os artrópodes hematófagos podem transmitir patógenos durante a sua alimentação e esses microorganismos parecem se beneficiar dos mecanismos moduladores da saliva, que facilitam a infecção do hospedeiro e o estabelecimento da doença (FONTAINE et al, 2011b;WASINPIYAMONGKOL et al, 2010). Além disso, esses patógenos são capazes de modular a composição da saliva e induzir mudanças comportamentais nos mosquitos resultando no aumento do seu potencial de transmissão (CHISENHALL et al, 2014;SIM;RAMIREZ;DIMOPOULOS, 2012 …”