| First Author | Won S | Year | 2012 |
| Journal | J Virol | Volume | 86 |
| Issue | 3 | Pages | 1802-8 |
| PubMed ID | 22114338 | Mgi Jnum | J:179383 |
| Mgi Id | MGI:5302143 | Doi | 10.1128/JVI.05660-11 |
| Citation | Won S, et al. (2012) Increased Susceptibility to DNA Virus Infection in Mice with a GCN2 Mutation. J Virol 86(3):1802-8 |
| abstractText | The downregulation of translation through eIF2alpha phosphorylation is a cellular response to diverse stresses, including viral infection, and is mediated by the GCN2 kinase, protein kinase R (PKR), protein kinase-like endoplasmic reticulum kinase (PERK), and heme-regulated inhibitor kinase (HRI). Although PKR plays a major role in defense against viruses, other eIF2alpha kinases also may respond to viral infection and contribute to the shutdown of protein synthesis. Here we describe the recessive, loss-of-function mutation atchoum (atc) in Eif2ak4, encoding GCN2, which increased susceptibility to infection by the double-stranded DNA viruses mouse cytomegalovirus (MCMV) and human adenovirus. This mutation was identified by screening macrophages isolated from mice carrying N-ethyl-N-nitrosourea (ENU)-induced mutations. Cells from Eif2ak4(atc/atc) mice failed to phosphorylate eIF2alpha in response to MCMV. Importantly, homozygous Eif2ak4(atc) mice showed a modest increase in susceptibility to MCMV infection, demonstrating that translational arrest dependent on GCN2 contributes to the antiviral response in vivo. |
