ArticlePLoS pathogens2016
A Single Amino Acid Dictates Protein Kinase R Susceptibility to Unrelated Viral Antagonists.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity.Nature communications · 2026Article
- Molecular Determinants of Species-Specific Interactions Between Protein Kinase R and Poxvirus K3 Orthologs.Viruses · 2025Article
- Viral interferon antagonism shapes host tropism.PLoS pathogens · 2025Review
- Poxvirus K3 Orthologs Regulate NF-κB-Dependent Inflammatory Responses by Targeting the PKR-eIF2α Axis in Multiple Species.Vaccines · 2025Article
- The battle between host antiviral innate immunity and immune evasion by cytomegalovirus.Cellular and molecular life sciences : CMLS · 2024Review
- Tanapox Virus and Yaba Monkey Tumor Virus K3 Orthologs Inhibit Primate Protein Kinase R in a Species-Specific Fashion.Viruses · 2024Article
- A single polymorphic residue in humans underlies species-specific restriction of HSV-1 by the antiviral protein MxB.bioRxiv : the preprint server for biology · 2023Article
- Antagonism of Protein Kinase R by Large DNA Viruses.Pathogens (Basel, Switzerland) · 2022Review
- Maladaptation after a virus host switch leads to increased activation of the pro-inflammatory NF-κB pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Minding the message: tactics controlling RNA decay, modification, and translation in virus-infected cells.Genes & development · 2022Review
- The herpesvirus accessory protein γ134.5 facilitates viral replication by disabling mitochondrial translocation of RIG-I.PLoS pathogens · 2021Article
- Orthopoxvirus K3 orthologs show virus- and host-specific inhibition of the antiviral protein kinase PKR.PLoS pathogens · 2021Article
- Species-Specific Host-Virus Interactions: Implications for Viral Host Range and Virulence.Trends in microbiology · 2020Review
- PKR inhibitors suppress endoplasmic reticulum stress and subdue glucolipotoxicity-mediated impairment of insulin secretion in pancreatic beta cells.Turkish journal of biology = Turk biyoloji dergisi · 2020Article
- Translational control during poxvirus infection.Wiley interdisciplinary reviews. RNA · 2019Review
- Translational Control in Virus-Infected Cells.Cold Spring Harbor perspectives in biology · 2019Review
- Species-specific inhibition of antiviral protein kinase R by capripoxviruses and vaccinia virus.Annals of the New York Academy of Sciences · 2019Article
- Inhibition of vaccinia virus replication by nitazoxanide.Virology · 2018Article
- Antagonism of the Protein Kinase R Pathway in Human Cells by Rhesus Cytomegalovirus.Journal of virology · 2018Article
- PKR: A Kinase to Remember.Frontiers in molecular neuroscience · 2018Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
During millions of years of coevolution with their hosts, cytomegaloviruses (CMVs) have succeeded in adapting to overcome host-specific immune defenses, including the protein kinase R (PKR) pathway. Consequently, these adaptations may also contribute to the inability of CMVs to cross species barriers. Here, we provide evidence that the evolutionary arms race between the antiviral factor PKR and its CMV antagonist TRS1 has led to extensive differences in the species-specificity of primate CMV TRS1 proteins. Moreover, we identify a single residue in human PKR that when mutated to the amino acid present in African green monkey (Agm) PKR (F489S) is sufficient to confer resistance to HCMVTRS1. Notably, this precise molecular determinant of PKR resistance has evolved under strong positive selection among primate PKR alleles and is positioned within the αG helix, which mediates the direct interaction of PKR with its substrate eIF2α. Remarkably, this same residue also impacts sensitivity to K3L, a poxvirus-encoded pseudosubstrate that structurally mimics eIF2α. Unlike K3L, TRS1 has no homology to eIF2α, suggesting that unrelated viral genes have convergently evolved to target this critical region of PKR. Despite its functional importance, the αG helix exhibits extraordinary plasticity, enabling adaptations that allow PKR to evade diverse viral antagonists while still maintaining its critical interaction with eIF2α.
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Registered trials
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.