LncRNA-SUSAJ1 Activates the ER Stress Pathway Inhibiting JEV Proliferation by Promoting PK15 Cells Apoptosis

Abstract

Background: Epidemic encephalitis B is a common zoonosis that threatens both pigs and humans. Effective prevention and control of epidemic encephalitis B is difficult. The cellular defence mechanism is closely related to the body's resistance to viral invasion. Long non-coding RNAs (lncRNAs) are involved in regulating various cellular activities. We previously found that lncRNA-SUSAJ1 could inhibit the proliferation of Japanese encephalitis virus (JEV). However, the mechanism underlying this suppression remains unclear. Methods: We performed Western blotting and quantitative reverse-transcription polymerase chain reaction (RT-qPCR) analyses, as well as mitochondrial membrane potential, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL), RNA pull-down, and RNA immunoprecipitation assays. Results: JC-1 cationic dye staining showed that lncRNA-SUSAJ1 promoted the depolarisation of mitochondrial membrane potential; H2DCFDA probe staining showed that lncRNA-SUSAJ1 enhanced the level of reactive oxygen species in PK15 porcine kidney cells. qRT-PCR and Western blotting revealed the expression levels of associated mRNAs and proteins, and the TUNEL and flow cytometry assays detected cell apoptosis. Their results showed that lncRNA-SUSAJ1 promoted the expression of pro-apoptotic genes and inhibited the expression of anti-apoptotic genes. RNA pull-down experiments using biotin-labelled lncRNA-SUSAJ1 showed colocalisation between lncRNA-SUSAJ1 and the 70 kDa heat shock protein (Hsp70). lncRNA-SUSAJ1 also activated unfolded protein response-related pathways, regulated protein degradation, and promoted apoptosis via the endoplasmic reticulum stress response, thereby inhibiting viral replication. Conclusions: The findings of this study provide insight into the specific molecular mechanism of lncRNA-SUSAJ1 resistance to viral proliferation by promoting cell apoptosis, clarify the antiviral effect of lncRNA-SUSAJ1 on JEV.

A translocation fluorescent probe for analyzing cellular physiological parameters in neurological disease models

“…52 During the infection process, viruses enter the host cells, which may lead to various problems such as changes in CMP, 53 inflammatory responses, and mitochondrial dysfunction. 54 Furthermore, when host cells continue to be infected, cell apoptosis may be triggered to limit the spread of the virus. 55 Therefore, monitoring the changes in the cell membrane and mitochondrial functions may provide potential early diagnostic markers, which can help in the early diagnosis of Japanese encephalitis and thus provide early treatment opportunities.…”

Unveiling the Hidden Regulators: The Impact of lncRNAs on Zoonoses

“…As for JEV infection, an increased expression of lncRNA-SUSAJ1 is observed as being regulated by the neuroinflammatory inducer CCR1/SP. LncRNA-SUSAJ1 , in turn hampers JEV replication and interrupts the transmission of JEV [ 115 , 116 ]. In addition, several broad-spectrum regulatory lncRNAs, such as JINR1 , ZAP-IT1 , MALAT1 , and Gm20559 , are characterized in flaviviral diseases [ 117 , 118 , 119 , 120 ].…”