Increased susceptibility to DNA virus infection in mice with a GCN2 mutation.
The downregulation of translation through eIF2α 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). Altho...
| Autors principals: | , , , , , , , , , |
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| Format: | Journal article |
| Idioma: | English |
| Publicat: |
2012
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| _version_ | 1826269223237713920 |
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| author | Won, S Eidenschenk, C Arnold, C Siggs, O Sun, L Brandl, K Mullen, T Nemerow, G Moresco, E Beutler, B |
| author_facet | Won, S Eidenschenk, C Arnold, C Siggs, O Sun, L Brandl, K Mullen, T Nemerow, G Moresco, E Beutler, B |
| author_sort | Won, S |
| collection | OXFORD |
| description | The downregulation of translation through eIF2α 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 eIF2α 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 eIF2α 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. |
| first_indexed | 2024-03-06T21:21:41Z |
| format | Journal article |
| id | oxford-uuid:41a6e9b5-57b1-4015-9d0b-2a415429b472 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:21:41Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:41a6e9b5-57b1-4015-9d0b-2a415429b4722022-03-26T14:44:58ZIncreased susceptibility to DNA virus infection in mice with a GCN2 mutation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:41a6e9b5-57b1-4015-9d0b-2a415429b472EnglishSymplectic Elements at Oxford2012Won, SEidenschenk, CArnold, CSiggs, OSun, LBrandl, KMullen, TNemerow, GMoresco, EBeutler, BThe downregulation of translation through eIF2α 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 eIF2α 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 eIF2α 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. |
| spellingShingle | Won, S Eidenschenk, C Arnold, C Siggs, O Sun, L Brandl, K Mullen, T Nemerow, G Moresco, E Beutler, B Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. |
| title | Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. |
| title_full | Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. |
| title_fullStr | Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. |
| title_full_unstemmed | Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. |
| title_short | Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. |
| title_sort | increased susceptibility to dna virus infection in mice with a gcn2 mutation |
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