Inhibition of eIF2α Phosphorylation by Peste des Petits Ruminant Virus Phosphoprotein Facilitates Viral Replication.

Xiaodong Qin,Xiangping Yin,Zhidong Zhang,Bang Qian,Yanmin Li,Meera Prajapati,Niyokwishimira Alfred,Yongxi Dou

doi:10.3389/fvets.2021.645571

Abstract

Peste des petits ruminant virus (PPRV) causes a highly contagious disease in small ruminants. The molecular mechanism of PPRV replication and its interactions with hosts are poorly studied. In other paramyxoviruses, the viral phosphoprotein (P) has been associated with multiple functions for key biological processes such as the regulation of transcription, translation, and the control of cell cycle. Phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) is an important process for gene regulation in host cells under stress, including viral infection. In the present study, molecular mechanisms associated with PPRV replication and viral interaction with host cells were investigated. We describe the ability of PPRV to dephosphorylate eIF2α and the potential of PPRV P protein to induce the host cellular growth arrest DNA damage protein (GADD34), which is known to be associated with eIF2α dephosphorylation. Furthermore, we observed that PPRV P protein alone could block PERK/eIF2α phosphorylation. We speculate that PPRV exploits eIF2α dephosphorylation to facilitate viral replication and that PPRV P protein is involved in this molecular mechanism. This work provides new insights into further understanding PPRV pathobiology and its viral/host interactions.

Highlights

Peste des petits ruminants (PPR) is a highly contagious disease of both domestic and wild small ruminants
We described the ability of Peste des petits ruminant virus (PPRV) to dephosphorylate eIF2α in Vero cells: a mechanism that may be important for PPRV to evade host immunity and facilitate viral replication
We demonstrated that PPRV P protein alone could block PERK/eIF2α phosphorylation and induce GADD34 upregulation

Summary

Introduction

Peste des petits ruminants (PPR) is a highly contagious disease of both domestic and wild small ruminants. The expression levels of P, V, and C proteins are likely regulated in the same way and the editing process regulates the levels of P and V proteins These functions suggest crucial roles for these proteins in facilitating virus replication by downregulating host immunity. Investigation of the molecular mechanisms and viral proteins involved in the modulation of cell fate during PPRV infection is required [8, 19]. This study was designed to investigate the molecular mechanism associated with PPRV replication and its viral/host interaction with a focus on eIF2α phosphorylation. We speculate that the repression of eIF2α phosphorylation by PPRV P protein via induction of cellular GADD34 expression is among the mechanisms conducted by PPRV to regulate long-term survival of host cells, which in turn is beneficial to virus replication

Methods

Results

Conclusion