Title : Crosstalk between Unfold Protein Response, autophagy and apoptosis in host cells infected with street rabies virus
Some researchers have investigated the effects of different strains of rabies virus in in vitro ,but the effects of nature circulating rabies virus have not been investigated in in vivo. Following cell infection, the virus takes over endoplasmic reticulum(ER), in order to deal with the virus destruction or elimination mechanisms. The response of ER to virus can be the activation unfolded protein response pathway, autophagy or apoptosis which is done by the cellular transcription factors such as Cas3, ATF6, ASK1 and CHOP. This study describes the changes that occur due to the infection of mouse brain cells with street rabies virus. We tested male NMRI mice in 7 groups. In the first to third groups, we injected virus, autophagy activator and inhibitor drugs via unilateral intracerebroventricular.
We injected pIRES-EGFP-Beclin1 12 hours before virus injection for group 4, when in group5 mice received street rabies virus and the vector simultaneously.Two last group received virus, vector and autophagy activator or inhibitor drugs. DFA was carried out on mouse brain tissue samples, total RNA was extracted and cDNA synthesized then samples were tested by qPCR to evaluate the expression of candidate genes. DFA test and comparisons with positive and negative controls confirmed viral infection and the Negri bodies were found as green fluorescent inclusion bodies within the cytoplasm of street rabies virus infected cells.ATF6, CHOP and ASK1 transcription factors in groups' 2, 3, and 6 showed a significant increase compared to the control group when Casp3 revealed a remarkable, increase in groups'2, 3, 4 and 5 (<0.05).
In rabies infection, IRE1α mediator is phosphorylated to splice XBP1 and convert it to an active form .Then XBP1along with ATF6 are induced CHOP expression which ultimately leads to apoptosis. Also, IRE1α could be activated ASK1 and autophagy while casp3 was caused only apoptosis. This study is showed that street rabies virus uses autophagy, apoptosis and activation of the UPR pathway to replicate itself and escape elimination and destruction by the host cell's mechanisms.
- Rabies infection causes stress and affects cellular organelles such as endoplasmic reticulum.
- The mechanisms of dealing with the virus in the brain of infected mouse cause the activation of some intracellular proteins that play the role of mediators in unfold protein response, autophagy and apoptosis pathways.
- Street rabies virus uses autophagy, apoptosis and UPR pathway to replicate itself and escape elimination and destruction by the host’s mechanisms.
- This research provides new information to help people infected with rabies infection.
- Understanding the mechanisms that the cell uses to fight the virus will help us design targeted treatments or choose an effective treatment method.
- This research can be used to expand the research or teaching of other faculties.