A novel p53 paralogue mediates antioxidant defense of mosquito cells to survive dengue virus replication

Abstract

Mosquito cells allow dengue viruses (DENVs) to undergo replication without causing serious deleterious effects on the cells, leading to advantages for dissemination to other cells. Despite this, increased accumulation of reactive oxygen species (ROS) is usually detected in C6/36 cells with DENV2 infection as shown in mammalian cells. Uniquely, oxidative stress caused by the ROS is alleviated by eliciting antioxidant defense which leads to protection of mosquito cells from the infection. In the present study, a novel p53 paralogue (p53-2) was identified and proved to be regulated in C6/36 cells with DENV2 infection. With a gene-knockdown technique, p53-2 was demonstrated to transcribe catalase which plays a critical role in reducing ROS accumulation and the death rate of infected cells. Ecologically, a higher survival rate of mosquito cells is a prerequisite for prosperous production of viral progeny, allowing infected mosquitoes to remain healthy and active for virus transmission.

A Peroxiredoxin From the Haemaphysalis longicornis Tick Affects Langat Virus Replication in a Hamster Cell Line

“…These results and reports also suggested that HlPrx2 proteins have a low possibility of being related to LGTV replication in the BHK cells. Chen et al (2018) reported that DENV replicates and induces ROS production in a mosquito-derived cell line without a cytopathic effect (CPE), while the infection of a mammalian cell line leads to cell death. Likewise, although LGTV infection of BHK cells induced CPE in the cells at Day 3 after inoculation, LGTV could replicate in an I. scapularis tick cell line (ISE6) without inducing CPE in the cells (Mlera et al, 2016).…”

Ambivalent Roles of Oxidative Stress in Triangular Relationships among Arthropod Vectors, Pathogens and Hosts

“…During dengue virus (DENV) infection, apoptosis is the usual outcome [ 60 ]. Apoptosis is usually brought about by the production of viral proteins, which disrupts the function of the endoplasmic reticulum (ER), resulting in the accumulation of misfolded and unfolded proteins.…”

“…The p53 is a transcription factor that selectively transcribes the catalase gene, which alleviates ROS accumulation within the cells, therefore reducing the rate of apoptosis ( Figure 1 B). In experiments that reduced the expression of the p53 gene, ROS accumulated in the infected cells [ 60 ]. In Ae.…”

Infection of Mammals and Mosquitoes by Alphaviruses: Involvement of Cell Death

“…The balance between a rapid apoptosis and a delayed, secondary necrosis may explain in part the differences between tolerant and resistant mosquitoes' strains. For more details see [177,[189][190][191][192][193][194][195][196] and Figure 3 for suggested mechanisms which may be involved in alphavirus infection in sensitive versus resistant mosquitoes, extrapolated from other arboviruses. In addition to the virus' ability to penetrate the cells of a particular mosquito (specific receptor, lipid membrane composition), the difference between resistant and tolerant strains may also lie in the rapidity of cell response to viral infection in the first targeted tissue, i.e., the mosquito gut.…”

“…Sensitive mosquitoes may tolerate viral infection through IAP-dependent apoptosis inhibition, as shown for the arbovirus bluetongue virus (BTV) [191,192]. Another tolerance mechanism to DENV seems to rely on resistance to oxidative stress through CAT protection in mosquito gut [193] or p53 isoforms regulation leading to cell survival in drosophila [194] and mosquito [195,196]. Delayed apoptosis may then lead to secondary necrosis, impairing a proper innate immune response, favoring basal lamina damage and viral spread [189].…”