Aedes aegypti Aag-2 Cell Proteome Modulation in Response to Chikungunya Virus Infection

Abstract

Chikungunya virus (CHIKV) is a single-stranded positive RNA virus that belongs to the genus Alphavirus and is transmitted to humans by infected Aedes aegypti and Aedes albopictus bites. In humans, CHIKV usually causes painful symptoms during acute and chronic stages of infection. Conversely, virus–vector interaction does not disturb the mosquito’s fitness, allowing a persistent infection. Herein, we studied CHIKV infection of Ae. aegypti Aag-2 cells (multiplicity of infection (MOI) of 0.1) for 48 h through label-free quantitative proteomic analysis and transmission electron microscopy (TEM). TEM images showed a high load of intracellular viral cargo at 48 h postinfection (hpi), as well as an unusual elongated mitochondria morphology that might indicate a mitochondrial imbalance. Proteome analysis revealed 196 regulated protein groups upon infection, which are related to protein synthesis, energy metabolism, signaling pathways, and apoptosis. These Aag-2 proteins regulated during CHIKV infection might have roles in antiviral and/or proviral mechanisms and the balance between viral propagation and the survival of host cells, possibly leading to the persistent infection.

Activation of innate immunity selectively compromises mitochondrial complex I, proline oxidation and flight activity in the major arbovirus vectorAedes aegypti

“…In this regard, the establishment of a resistant phenotype against Plasmodium infection involve reduced OXPHOS and increased mitochondrial oxidant production indicating that regulation of mitochondrial energy metabolism control the susceptibility of insect vector to infection (Oliveira et al, 2011). In addition, dynamic modulation of metabolic enzymes during infections was reported during mosquito infection suggesting that bioenergetic mechanisms that supply electrons to OXPHOS play a role in the adaptive vector response against infectious challenges (Martins et al, 2021;Santana-Román et al, 2021;Vasconcellos et al, 2022Vasconcellos et al, , 2020. The results observed in the present work raise the question on what are the metabolic consequences to flight dispersal of an infected A. aegypti female.…”

“…Also, refractoriness to Plasmodium infection is associated with strong reductions in OXPHOS in Anopheles gambiae mosquitoes (Oliveira et al, 2011). Large-scale quantitative proteomic studies during arboviral infection have shown remarkable changes in the expression of key metabolic enzymes including those involved in glycolysis, tricarboxylic acid cycle, and OXPHOS (Martins et al, 2021;Vasconcellos et al, 2022Vasconcellos et al, , 2020. However, direct evidence demonstrating alterations on insect mitochondrial function resulting from immune activation remains largely obscure.…”

Controlling arbovirus infection: high-throughput transcriptome and proteome insights

“…While A. aegypti is the predominant model used, the strains vary among studies. Proteomic data is also accessible for A. albopictus and for three major mosquito cell lines, U4.4 ( Kumar et al, 2022 ) and C6/36 ( Patramool et al, 2011 ; Zhang et al, 2013 ; Lee and Chu, 2015 ; Saucereau et al, 2017 ; Xin et al, 2017 ) (both derived from A. albopictus ) and Aag2 ( Vasconcellos et al, 2020 , 2022 ) (derived from A. aegypti ). Among the studied arboviruses, CHIKV, followed by DENV-2 and ZIKV have been the most extensively examined.…”

“…The proteome analyses show that numerous cellular pathways are affected during viral infection, with a predominant pattern of protein downregulation ( Chisenhall et al, 2014b ; Saucereau et al, 2017 ; Vasconcellos et al, 2022 ). Despite variations in research findings between studies, a consensus emerges regarding the substantial alteration of immune-related factors ( Tchankouo-Nguetcheu et al, 2010 ; Chisenhall et al, 2014b ; Xin et al, 2017 ; Vasconcellos et al, 2020 ), particularly those linked to the Toll-like receptor pathway.…”

A Review of Omics Studies on Arboviruses: Alphavirus, Orthobunyavirus and Phlebovirus

“…aegypti Aag-2 cells revealed a total of 196 regulated proteins related to energy metabolism, protein synthesis, signalling pathways and apoptosis, with antiviral and proviral effects. A known mechanism to control viral propagation was observed with the shutoff of general protein synthesis in a 48 h post-infection period and the induction of autophagy by ROS (Reactive oxygen species) production in mitochondrial nets to delay apoptosis and prolong survival of the infected cells before apoptosis [ 96 ].…”