Mohr Lab
Research Interests
Figure 1. The production of double-stranded RNA (dsRNA) in viral infected cells results in the activation of the cellular PKR kinase. PKR is normally present in an inactive state until an activating ligand is encountered. Binding of dsRNA to PKR leads to the assembly of a PKR dimer whereupon each subunit phosphorylates the other, activating the enzyme and enabling it to phosphorylate the alpha subunit of eIF2, a critical translation initiation factor.
Protein synthesis is inhibited (red pathways) because phosphorylated eIF2 cannot function in the initiation reaction. To prevent the accumulation of phosphorylated eIF2a, herpes simplex virus encodes at least two separate functions. The gamma 34.5 protein is a regulatory subunit for the cellular protein phosphatase 1a (PP1a) catalytic subunit. The PP1a -gamma 34.5 complex removes the phosphate from eIF2a, thus restoring pools of active, unphosphorylated eIF2a in the cell. In addition, the viral Us11 polypeptide is a double strand RNA binding protein that can prevent the activation of the cellular PKR kinase. Both of these pathways are shown in green as they allow for continued protein synthesis. Functions designed to override the cellular antiviral response enable the virus to complete its lifecycle, culminating in the assembly and release of viral progeny.
Research Interests
Figure 1. The production of double-stranded RNA (dsRNA) in viral infected cells results in the activation of the cellular PKR kinase. PKR is normally present in an inactive state until an activating ligand is encountered. Binding of dsRNA to PKR leads to the assembly of a PKR dimer whereupon each subunit phosphorylates the other, activating the enzyme and enabling it to phosphorylate the alpha subunit of eIF2, a critical translation initiation factor.
Protein synthesis is inhibited (red pathways) because phosphorylated eIF2 cannot function in the initiation reaction. To prevent the accumulation of phosphorylated eIF2a, herpes simplex virus encodes at least two separate functions. The gamma 34.5 protein is a regulatory subunit for the cellular protein phosphatase 1a (PP1a) catalytic subunit. The PP1a -gamma 34.5 complex removes the phosphate from eIF2a, thus restoring pools of active, unphosphorylated eIF2a in the cell. In addition, the viral Us11 polypeptide is a double strand RNA binding protein that can prevent the activation of the cellular PKR kinase. Both of these pathways are shown in green as they allow for continued protein synthesis. Functions designed to override the cellular antiviral response enable the virus to complete its lifecycle, culminating in the assembly and release of viral progeny.