Oxidative stress specifically inhibits replication of dengue virus

Abstract

Reactive oxygen species (ROS) are chemically active species which are involved in maintaining cellular and signalling processes at physiological concentrations. Therefore, cellular components that regulate redox balance are likely to play a crucial role in viral life-cycle either as promoters of viral replication or with antiviral functions. Zinc is an essential micronutrient associated with anti-oxidative systems and helps in maintaining a balanced cellular redox state. Here, we show that zinc chelation leads to induction of reactive oxygen species (ROS) in epithelial cells and addition of zinc restores ROS levels to basal state. Addition of ROS (H2O2) inhibited dengue virus (DENV) infection in a dose-dependent manner indicating that oxidative stress has adverse effects on DENV infection. ROS affects early stages of DENV replication as observed by quantitation of positive and negative strand viral RNA. We observed that addition of ROS specifically affected viral titres of positive strand RNA viruses. We further demonstrate that ROS specifically altered SEC31A expression at the ER suggesting a role for SEC31A-mediated pathways in the life-cycle of positive strand RNA viruses and provides an opportunity to identify drug targets regulating oxidative stress responses for antiviral development.

Infection of Endothelial Cells by Dengue Virus Induces ROS Production by Different Sources Affecting Virus Replication, Cellular Activation, Death and Vascular Permeability

“…Despite possible antiviral effects of oxidative stress responses (49,50), we observed that ROS inhibition reduced DENV replication in HBMEC. Different mechanisms might explain this phenomenon.…”

Impact of CHIKV Replication on the Global Proteome of Aedes albopictus Cells

“…The cells were able to tolerate the virus to the late infection time points, indicating that the virus is persistently replicating inside the Aedes cells, corroborating earlier reports involving other arboviruses such as Sindbis virus, Culex Y virus, and West Nile virus [ 44 , 45 , 46 ]. Viruses are known to induce oxidative stress in host cells, which can have both pro-viral and antiviral impacts on the cells [ 38 , 47 , 48 ]. Either way, this oxidative stress leads to activation of pathways such as apoptosis, as well as downregulation of pathways such as translation, and RNA processing, which is often associated with the formation of RNP complexes called stress granules [ 49 ].…”

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

“…As part of a central role in the viral replication and oxidative stress, the (dys)function of host mitochondria seems to be an essential element for many viruses ( El-Bacha and Da Poian, 2013 ). For instance, an enhanced level of ROS inhibits DENV infection ( Khan et al., 2021 ). In the ZIKV, this ROS imbalance is associated with mitochondrial and DNA damage in human astrocytes ( Ledur et al., 2020 ).…”

“…In the ZIKV, this ROS imbalance is associated with mitochondrial and DNA damage in human astrocytes ( Ledur et al., 2020 ). In both cases, the use of fluorescent probes against free radicals, such as 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) and dihydroethidium (DHE), were respectively used ( Ledur et al., 2020 ; Khan et al., 2021 ). Perhaps novel studies regarding free radicals production upon CHIKV infection could cast a glance on whether the same phenomena could take place in Aag-2 insect cells.…”