Autophagy and Unfolded Protein Response Induction: Crosstalk between Street Rabies Virus and Host

Abstract

Abstract The endoplasmic reticulum (ER) is a multifunctional organelle that responds to cellular stress. ER response mechanism is mediated by unfolded protein response (UPR) or ER-associated degradation (ERAD) pathway. Depending on the host cell type and virus, viral infections could cause stress to the ER, activate or inhibit autophagy. Autophagy is a conserved dissociation process during growth, differentiation, survival, etc. We decided to infect the mouse brain’s tissues with street rabies virus (SRABV) and study some transcription factors involved in ER stress and autophagy. Total RNA was extracted from the tissue, and cDNA was synthesized. Using specific primers, the real-time PCR was performed. The expression of Hprt, CCAATenhancer-binding protein homologous protein (CHOP), Apoptosis signal-regulating kinase1 (Ask-1), Transcription factor 6(ATF-6) and Caspase 3(Casp3) genes were examined. SRABV has increased the significant changes in mRNA expression of ATF-6, CHOP, and Ask-1 in the control group (group V) in the brain of infected mice (p < 0.05). Induction or inhibition of drug-induced autophagy (Rapamycin and 3-methyl adenine) in infected cells (group R &T) is caused ER stress and made tremendous changes in all ATF-6, CHOP, Ask-1 and Casp3. Treatment with pIRES-EGFP-beclin1vector and rapamycin in infected cells (group D) is caused by changes in all parameters except Casp3. An increase in Casp3 is observed only when the vector and virus are injected together into the cells (group B). Autophagy and protection against cell death result from SRABV infection by activating the ER stress pathways, followed by a marked increase in ATF-6, CHOP, Ask-1, and Casp3 levels.