Chikungunya virus infection in Aedes aegypti is modulated by L-cysteine, taurine, hypotaurine and glutathione metabolism

Abstract

Background

Blood meal and infections cause redox imbalance and oxidative damage in mosquitoes which triggers the mosquito’s system to produce antioxidants in response to increased oxidative stress. Important pathways activated owing to redox imbalance include taurine, hypotaurine and glutathione metabolism. The present study was undertaken to evaluate the role of these pathways during chikungunya virus (CHIKV) infection in Aedes aegypti mosquitoes.

Methodology

Using a dietary L-cysteine supplement system, we upregulated these pathways and evaluated oxidative damage and oxidative stress response upon CHIKV infection using protein carbonylation and GST assays. Further, using a dsRNA based approach, we silenced some of the genes involved in synthesis and transport of taurine and hypotaurine and then evaluated the impact of these genes on CHIKV infection and redox biology in the mosquitoes.

Conclusions

We report that CHIKV infection exerts oxidative stress in the A. aegypti, leading to oxidative damage and as a response, an elevated GST activity was observed. It was also observed that dietary L-cysteine treatment restricted CHIKV infection in A. aegypti mosquitoes. This L-cysteine mediated CHIKV inhibition was coincided by enhanced GST activity that further resulted in reduced oxidative damage during the infection. We also report that silencing of genes involved in synthesis of taurine and hypotaurine modulates CHIKV infection and redox biology of Aedes mosquitoes during the infection.

Author summary

Mosquitoes need human blood for the development of their eggs. During this process, when the mosquito bites human already harboring viruses such as chikungunya virus (CHIKV), the virus is taken up by the mosquito, which carries the virus for the rest of its life and transmits the virus to healthy individuals during subsequent blood meals. However, the impact of these viruses on the mosquito physiology is poorly understood. This study is an attempt to evaluate the impact of CHIKV infection on the redox biology of Aedes mosquitoes. Oxidative stress is a critical response to several biological activities and is controlled by a vast network of pathways of genes/proteins. Some of these pathways are L-cysteine centric, such as taurine, hypotaurine and glutathione metabolism. By providing dietary supplements of L-cysteine and by reducing the expression of some of the genes in the above mentioned pathways, we studied the role of these pathways in regulating oxidative stress during CHIKV infection. Our results suggest that dietary supplement of L-cysteine and selected genes of the taurine/hypotaurine and glutathione pathways was found to control oxidative damage in the mosquitoes during CHIKV infection by regulating the expression of Glutathione-s-transferases (GST) enzyme, a well known antioxidant molecule.