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

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.