Additive Protection by Antioxidant and Apoptosis-Inhibiting Effects on Mosquito Cells with Dengue 2 Virus Infection

Abstract

Cytopathic effects (CPEs) in mosquito cells are generally trivial compared to those that occur in mammalian cells, which usually end up undergoing apoptosis during dengue virus (DENV) infection. However, oxidative stress was detected in both types of infected cells. Despite this, the survival of mosquito cells benefits from the upregulation of genes related to antioxidant defense, such as glutathione S transferase (GST). A second defense system, i.e., consisting of antiapoptotic effects, was also shown to play a role in protecting mosquito cells against DENV infection. This system is regulated by an inhibitor of apoptosis (IAP) that is an upstream regulator of caspases-9 and -3. DENV-infected C6/36 cells with double knockdown of GST and the IAP showed a synergistic effect on activation of these two caspases, causing a higher rate of apoptosis (>20%) than those with knockdown of each single gene (∼10%). It seems that the IAP acts as a second line of defense with an additional effect on the survival of mosquito cells with DENV infection. Compared to mammalian cells, residual hydrogen peroxide in DENV-infected C6/36 cells may signal for upregulation of the IAP. This novel finding sheds light on virus/cell interactions and their coevolution that may elucidate how mosquitoes can be a vector of DENV and probably most other arboviruses in nature.

Altered mitochondrial dynamics as a consequence of Venezuelan Equine encephalitis virus infection

“…[31][32][33] It is therefore of relevance to determine if VEEV infection will impact insect cells and lead to accumulation of ROS in a similar manner as we observed in U87MG cells. We studied whether infection of mosquito cells with TC-83 would lead to a disruption of mitochondrial function.…”

“…It has been demonstrated that in the case of flavivirus infections, infected insect cells show changes in antioxidant mechanisms that decrease the extent of cell death. [31][32][33] It has been demonstrated for Dengue virus that infected mosquito cells mounted a stronger antioxidant response by synthesising antioxidant enzymes (elevation of Glutathione S-transferase activity). 48 Mitochondrial distribution in cells and mitochondrial mobility are essential features of healthy cells.…”

Cytoarchitecture of Zika virus infection in human neuroblastoma and Aedes albopictus cell lines

“…Staining for cleaved caspase 3 was first noted at 48 hpi in these cells and was evident at later times points, too; however, only rare mosquito cells were TUNEL positive from 72–120 hpi, indicating that widespread frank apoptosis was not induced. Although we have not investigated these findings, the lack of apoptosis in ZIKV-infected C6/36 cells may be related to upregulation of inhibitor of apoptosis (IAP) genes which have been shown to be operative in Dengue 2 virus-infected C6/36 cells (43) or, perhaps, through inhibition of a molecule downstream of caspase-3 within the apoptosis pathway. Further studies into ZIKV infection and the apoptotic pathway in mosquito cells are required to better understand the role of caspase activation and cell death.…”

RNAi reveals proteins for metabolism and protein processing associated with Langat virus infection in Ixodes scapularis (black-legged tick) ISE6 cells

“…Flaviviruses are thought to exploit the cellular stress response to aid replication [51] and oxidative stress is thought to aid the replication of positive-strand RNA viruses [52]. Further, it has been proposed that the balance between antioxidant responses maintains an anti-apoptotic environment during flavivirus infection of the cell [53, 54], presumably facilitating virus replication and transmission.…”