Increased susceptibility to DNA virus infection in mice with a GCN2 mutation

Sungyong Won, Celine Eidenschenk, Carrie N. Arnold, Owen M. Siggs, Lei Sun, Katharina Brandl, Tina Marie Mullen, Glen R. Nemerow, Eva Marie Y Moresco, Bruce Beutler

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The downre gulation 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-offunction 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 Eif2ak4atc/atc mice failed to phosphorylate eIF2α in response to MCMV. Importantly, homozygous Eif2ak4atc mice showed a modest increase in susceptibility to MCMV infection, demonstrating that translational arrest dependent on GCN2 contributes to the antiviral response in vivo.

Original languageEnglish (US)
Pages (from-to)1802-1808
Number of pages7
JournalJournal of Virology
Volume86
Issue number3
DOIs
StatePublished - Feb 2012

Fingerprint

DNA Virus Infections
Murid herpesvirus 1
DNA viruses
Muromegalovirus
phosphotransferases (kinases)
Phosphotransferases
protein kinases
Protein Kinases
mutation
Mutation
mice
Virus Diseases
infection
N-ethyl-N-nitrosourea
dsDNA viruses
Ethylnitrosourea
Human Adenoviruses
DNA Viruses
Cytomegalovirus Infections
heme

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Won, S., Eidenschenk, C., Arnold, C. N., Siggs, O. M., Sun, L., Brandl, K., ... Beutler, B. (2012). Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. Journal of Virology, 86(3), 1802-1808. https://doi.org/10.1128/JVI.05660-11

Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. / Won, Sungyong; Eidenschenk, Celine; Arnold, Carrie N.; Siggs, Owen M.; Sun, Lei; Brandl, Katharina; Mullen, Tina Marie; Nemerow, Glen R.; Moresco, Eva Marie Y; Beutler, Bruce.

In: Journal of Virology, Vol. 86, No. 3, 02.2012, p. 1802-1808.

Research output: Contribution to journalArticle

Won, S, Eidenschenk, C, Arnold, CN, Siggs, OM, Sun, L, Brandl, K, Mullen, TM, Nemerow, GR, Moresco, EMY & Beutler, B 2012, 'Increased susceptibility to DNA virus infection in mice with a GCN2 mutation', Journal of Virology, vol. 86, no. 3, pp. 1802-1808. https://doi.org/10.1128/JVI.05660-11
Won S, Eidenschenk C, Arnold CN, Siggs OM, Sun L, Brandl K et al. Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. Journal of Virology. 2012 Feb;86(3):1802-1808. https://doi.org/10.1128/JVI.05660-11
Won, Sungyong ; Eidenschenk, Celine ; Arnold, Carrie N. ; Siggs, Owen M. ; Sun, Lei ; Brandl, Katharina ; Mullen, Tina Marie ; Nemerow, Glen R. ; Moresco, Eva Marie Y ; Beutler, Bruce. / Increased susceptibility to DNA virus infection in mice with a GCN2 mutation. In: Journal of Virology. 2012 ; Vol. 86, No. 3. pp. 1802-1808.
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