The cellular metabolome plays a key role in determining the outcome of dengue virus replication in the mosquito vector. A fine balance between metabolic commensalism versus competition must occur for efficient viral entry, replication, virus assembly and dissemination within different mosquito tissues prior to transmission to a new host. These requirements are exacerbated by the influence of endosymbiotic microbiota (such as Wolbachia), various ecological conditions and the age of the vector. Dengue viruses (DENV) cause 400 million infections a year and are transmitted primarily by Aedes aegypti mosquitoes. In this study, we used high-resolution mass spectrometry to explore the temporal metabolic changes following infection with DENV type 2 in the midgut of A. aegypti mosquitoes. We found significant fluctuations in the expression of several lipid classes. Specifically, a temporal increase in the expression of phosphoglycerolipids, which are major components of cellular membranes, was coincident with active viral replication in the midgut. Certain sphingolipids, which are highly bioactive effectors, were also elevated in expression during early times post-infection. In addition, evidence of disrupted mitochondrial function and possible diversion to glycolysis was identified. Interestingly, we have also discovered that other viruses such as Zika and Chikungunya also transmitted by the same vector don’t share the same metabolic requirements. This observation sheds light on why co-infection with several of these viruses is possible. We are now exploring the mechanisms of how DENV exploits these metabolic pathways and identifying the key effectors in each pathway that are required for efficient DENV replication in the mosquito and transmission to a new human host. We will highlight metabolic control points that could be targeted for novel intervention avenues.

Flipping metabolism: Controlling viral disease transmission and pathogenesis

ACS Fall 2020 Virtual Meeting

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