Induction of the unfolded protein response (UPR) during Marek's disease virus (MDV) infection

• Published in: Virology (New York, N.Y.) Vol. 522; pp. 1 - 12
• Main Authors: Neerukonda, Sabari Nath, Katneni, Upendra K., Bott, Matthew, Golovan, Serguei P., Parcells, Mark S.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2018
• Subjects: Activating transcription factor 6 (ATF6); Endoplasmic reticulum stress; Inositol-requiring protein 1 alpha (IRE1α); Lymphomas; Marek's disease virus; Protein kinase R – like endoplasmic reticulum kinase (PERK); Unfolded protein response; Marek's disease virus; Inositol-requiring protein 1 alpha (IRE1α); Activating transcription factor 6 (ATF6); Lymphomas; Protein kinase R – like endoplasmic reticulum kinase (PERK); Endoplasmic reticulum stress; Unfolded protein response
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2018.06.016

Marek's disease (MD) is a pathology of chickens associated with paralysis, immune suppression, and the rapid formation of T-cell lymphomas. MD is caused by the herpesvirus, Marek's disease virus (MDV). We examined endoplasmic reticulum (ER) stress and the activation of unfolded protein response (UPR) pathways during MDV infection of cells in culture and lymphocytes in vivo. MDV strains activate the UPR as measured by increased mRNA expression of GRP78/BiP with concomitant XBP1 splicing and induction of its target gene, EDEM1. Cell culture replication of virulent, but not vaccine MDVs, activated the UPR at late in infection. Pathotype-associated UPR activation was induced to a greater level by a vv + MDV. Discrete UPR activation was observed during MDV in vivo infection, with the level of UPR modulation being affected by the MDV oncoprotein Meq. Finally, ATF6 was found to be activated in vv + MDV-induced primary lymphomas, suggesting a possible role in tumor progression.
•MDV infection activates the UPR in cell culture and in vivo.•Virulent MDVs, but not vaccine MDVs, activate the UPR.•Discrete UPR pathway activation is seen during various infection stages in vivo.•The extent of pathway activation in vivo appears to be regulated by the MDV primary bZIP oncoprotein Meq.