ArticleGenes & development2006
Translational resistance of late alphavirus mRNA to eIF2alpha phosphorylation: a strategy to overcome the antiviral effect of protein kinase PKR.
Article in Genes & development, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 138 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
138 citing papers in PubMed, 206 citations in OpenAlex.
- The pathogenicity and virulence of Sindbis virus.Virulence · 2026Review
- Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.Nucleic acids research · 2026Article
- Ewing sarcoma breakpoint region 1 (EWSR1) protein binds to nonstructural protein 2 and non-coding regions of chikungunya virus genome to inhibit virus replication.Journal of virology · 2026Article
- Stress granules formed during infections with RNA viruses have significant virus-specific differences in generation and composition.PLoS biology · 2026Article
- Alphavirus replicase and regulatory RNA elements in host interactions and viral vector engineering.Journal of virology · 2026Review
- Altered neuronal start codon stringency favors cap-independent repeat-associated non-AUG translation.bioRxiv : the preprint server for biology · 2026Article
- Reprogramming innate immunity through viral interference: A double-edged strategy for enhancing and containing gene therapies.Molecular therapy. Nucleic acids · 2026Review
- Translational repression of viral RNAs supports persistent arbovirus infection in mosquitoes.PLoS biology · 2026Article
- Engineered VPg saRNA achieves cap-independent, low-immunogenic and precise encoding of therapeutic proteins in vivo.Nature communications · 2026Article
- eIF2A regulates cell migration in a translation-independent manner.Science advances · 2025Article
- Functional RNA Elements in Alphavirus Genomes.Current microbiology · 2025Review
- A conserved opal termination codon optimizes a temperature-dependent trade-off between protein production and processing in alphaviruses.Science advances · 2025Article
- Nuclear RNA-binding proteins meet cytoplasmic viruses.RNA (New York, N.Y.) · 2025Review
- Host-like RNA Elements Regulate Virus Translation.Viruses · 2024Review
- Translational Control of Alphavirus-Host Interactions: Implications in Viral Evolution, Tropism and Antiviral Response.Viruses · 2024Review
- Yeast eIF2A has a minimal role in translation initiation and uORF-mediated translational control in vivo.eLife · 2024Article
- Increased levels of eIF2A inhibit translation by sequestering 40S ribosomal subunits.Nucleic acids research · 2023Article
- Next generation self-replicating RNA vectors for vaccines and immunotherapies.Cancer gene therapy · 2023Review
- Susceptibility and Permissivity of Zebrafish (Viruses · 2023Article
- Article
78 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The double-stranded RNA-dependent protein kinase (PKR) is one of the four mammalian kinases that phosphorylates the translation initiation factor 2alpha in response to virus infection. This kinase is induced by interferon and activated by double-stranded RNA (dsRNA). Phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha) blocks translation initiation of both cellular and viral mRNA, inhibiting virus replication. To counteract this effect, most viruses express inhibitors that prevent PKR activation in infected cells. Here we report that PKR is highly activated following infection with alphaviruses Sindbis (SV) and Semliki Forest virus (SFV), leading to the almost complete phosphorylation of eIF2alpha. Notably, subgenomic SV 26S mRNA is translated efficiently in the presence of phosphorylated eIF2alpha. This modification of eIF2 does not restrict viral replication; SV 26S mRNA initiates translation with canonical methionine in the presence of high levels of phosphorylated eIF2alpha. Genetic and biochemical data showed a highly stable RNA hairpin loop located downstream of the AUG initiator codon that is necessary to provide translational resistance to eIF2alpha phosphorylation. This structure can stall the ribosomes on the correct site to initiate translation of SV 26S mRNA, thus bypassing the requirement for a functional eIF2. Our findings show the existence of an alternative way to locate the ribosomes on the initiation codon of mRNA that is exploited by a family of viruses to counteract the antiviral effect of PKR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.