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

<i>Morbillivirus canis</i>, commonly named Canine distemper virus (CDV), is a morbillivirus implicated in several signs in the <i>Canidae</i> family. In dogs (<i>Canis lupus familiaris</i>), common signs of infection include conjunctivitis, digital hyperkeratosis...

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Main Authors: Santiago Emanuel Colina, Macarena Marta Williman, Marco Antonio Tizzano, María Soledad Serena, María Gabriela Echeverría, Germán Ernesto Metz
Format: Article
Language:English
Published: MDPI AG 2024-11-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/16/12/1846
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author Santiago Emanuel Colina
Macarena Marta Williman
Marco Antonio Tizzano
María Soledad Serena
María Gabriela Echeverría
Germán Ernesto Metz
author_facet Santiago Emanuel Colina
Macarena Marta Williman
Marco Antonio Tizzano
María Soledad Serena
María Gabriela Echeverría
Germán Ernesto Metz
author_sort Santiago Emanuel Colina
collection DOAJ
description <i>Morbillivirus canis</i>, commonly named Canine distemper virus (CDV), is a morbillivirus implicated in several signs in the <i>Canidae</i> family. In dogs (<i>Canis lupus familiaris</i>), common signs of infection include conjunctivitis, digital hyperkeratosis and neuropathologies. Even with vaccination, the canine distemper disease persists worldwide so the molecular pathways implicated in the infection processes have been an interesting and promising area in new therapeutic drugs research in recent years. It is known that in the process of virus infection, the endoplasmic reticulum (ER) loses its homeostasis, inducing stress and the subsequent unfolded protein response or UPR in which three ER-trans-membrane proteins are implicated: PERK, IRE1 and ATF6. Moreover, in prolonged ER stress, the apoptosis is induced through the CHOP, as a final step of viral infection. Cell culture and molecular techniques such 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 the p38 protein and the apoptotic CHOP was demonstrated to contribute to the process of infection. Even more, our study suggested that CDV replication occurs in a PERK-dependent manner.
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spelling doaj-art-13e0bdd7ae6444adbe8a7fbea286f41a2024-12-27T14:59:01ZengMDPI AGViruses1999-49152024-11-011612184610.3390/v16121846Morbillivirus Canis Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and ApoptosisSantiago Emanuel Colina0Macarena Marta Williman1Marco Antonio Tizzano2María Soledad Serena3María Gabriela Echeverría4Germán Ernesto Metz5Laboratorio de Virología, Centro de Microbiología Básica y Aplicada (CEMIBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata CP 1900, Buenos Aires, ArgentinaLaboratorio de Virología, Centro de Microbiología Básica y Aplicada (CEMIBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata CP 1900, Buenos Aires, ArgentinaLaboratorio de Virología, Centro de Microbiología Básica y Aplicada (CEMIBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata CP 1900, Buenos Aires, ArgentinaLaboratorio de Virología, Centro de Microbiología Básica y Aplicada (CEMIBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata CP 1900, Buenos Aires, ArgentinaLaboratorio de Virología, Centro de Microbiología Básica y Aplicada (CEMIBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata CP 1900, Buenos Aires, ArgentinaLaboratorio de Virología, Centro de Microbiología Básica y Aplicada (CEMIBA), Facultad de Ciencias Veterinarias, Universidad Nacional de La Plata, La Plata CP 1900, Buenos Aires, Argentina<i>Morbillivirus canis</i>, commonly named Canine distemper virus (CDV), is a morbillivirus implicated in several signs in the <i>Canidae</i> family. In dogs (<i>Canis lupus familiaris</i>), common signs of infection include conjunctivitis, digital hyperkeratosis and neuropathologies. Even with vaccination, the canine distemper disease persists worldwide so the molecular pathways implicated in the infection processes have been an interesting and promising area in new therapeutic drugs research in recent years. It is known that in the process of virus infection, the endoplasmic reticulum (ER) loses its homeostasis, inducing stress and the subsequent unfolded protein response or UPR in which three ER-trans-membrane proteins are implicated: PERK, IRE1 and ATF6. Moreover, in prolonged ER stress, the apoptosis is induced through the CHOP, as a final step of viral infection. Cell culture and molecular techniques such 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 the p38 protein and the apoptotic CHOP was demonstrated to contribute to the process of infection. Even more, our study suggested that CDV replication occurs in a PERK-dependent manner.https://www.mdpi.com/1999-4915/16/12/1846canine distemper virusER stressUPR pathwaysapoptosis
spellingShingle Santiago Emanuel Colina
Macarena Marta Williman
Marco Antonio Tizzano
María Soledad Serena
María Gabriela Echeverría
Germán Ernesto Metz
Morbillivirus Canis Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and Apoptosis
Viruses
canine distemper virus
ER stress
UPR pathways
apoptosis
title Morbillivirus Canis Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and Apoptosis
title_full Morbillivirus Canis Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and Apoptosis
title_fullStr Morbillivirus Canis Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and Apoptosis
title_full_unstemmed Morbillivirus Canis Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and Apoptosis
title_short Morbillivirus Canis Infection Induces Activation of Three Branches of Unfolded Protein Response, MAPK and Apoptosis
title_sort morbillivirus canis infection induces activation of three branches of unfolded protein response mapk and apoptosis
topic canine distemper virus
ER stress
UPR pathways
apoptosis
url https://www.mdpi.com/1999-4915/16/12/1846
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