Canine Morbillivirus Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and Apoptosis

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Abstract

The canine distemper virus (CDV) is a morbillivirus implicated in several signs in the Canidae family, in dogs, conjunctivitis, digital hyperkeratosis and neuropathologies are common signs of its infection. Even with the existing vaccination, the canine distemper disease persists worldwide so the molecular pathways implicated in the infection processes has been an interesting and promisor area in the new therapeutic drugs research over recent years. It is known that in the process of virus infection the endoplasmic reticulum organelle lost its homeostasis inducing stress and the subsequence unfolded protein response or UPR in which three ER-trans-membrane proteins are implicated: PERK, IRE1 and ATF6. Moreover, in a prolonged ER stress the apoptosis dead are induced through CHOP protein, as a final step of virus infections. Molecular and cell culture techniques as RT-qPCR and RT-PCR were used in the present study. We demonstrate the activation in vitro of the three UPR pathways after infection with an attenuated strain of CDV. Also, the implication of a MAPK pathway through p38 protein and the apoptotic protein CHOP was funded to participate in all times of infection. Even more, our study suggested that CDV replication occur in a PERK-dependent manner.

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