ArticlePLoS pathogens2021
Orthopoxvirus K3 orthologs show virus- and host-specific inhibition of the antiviral protein kinase PKR.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 48 citations in OpenAlex.
- Monkeypox virus replication and host response in vaginal and ectocervical epithelial cells.Virulence · 2026Article
- Current Strategies for Selecting Recombinant Orthopoxvirus Proteins for Immunobiological and Diagnostic Applications.Viruses · 2026Review
- Exploration of the protein and pharmacological landscape of monkeypox virus treatment: from entry point to end point.Molecular diversity · 2026Review
- The strategies and advances of mRNA translation booster.Asian journal of pharmaceutical sciences · 2025Review
- Molecular Determinants of Species-Specific Interactions Between Protein Kinase R and Poxvirus K3 Orthologs.Viruses · 2025Article
- Lumpy Skin Disease Virus Pathogenesis: Viral Protein Functions and Comparative Insights from Vaccinia Virus.Animals : an open access journal from MDPI · 2025Review
- 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
- Review
- A poxvirus ankyrin protein LSDV012 inhibits IFIT1 in a host-species-specific manner by compromising its RNA binding ability.PLoS pathogens · 2025Article
- Monoclonal Antibodies in Light of Mpox Outbreak: Current Research, Therapeutic Targets, and Animal Models.Antibodies (Basel, Switzerland) · 2025Review
- Regulation of innate immunity by liquid-liquid phase separation: a focus on veterinary viruses.Frontiers in microbiology · 2025Review
- Proteome-wide characterization of PTMs reveals host cell responses to viral infection and identifies putative antiviral drug targets.Frontiers in immunology · 2025Review
- Protein Kinase R (PKR) as a Novel dsRNA Sensor in Antiviral Innate Immunity.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Review
- Host species-specific activity of the poxvirus PKR inhibitors E3 and K3 mediate host range function.Journal of virology · 2024Article
- Article
- MPXV infection impairs IFN response but is partially sensitive to IFN-γ antiviral effect.Medical microbiology and immunology · 2024Article
- The unique immune evasion mechanisms of the mpox virus and their implication for developing new vaccines and immunotherapies.Virologica Sinica · 2024Review
- Systematic genetic characterization of the human PKR kinase domain highlights its functional malleability to escape a poxvirus substrate mimic.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The antiviral protein kinase R (PKR) is an important host restriction factor, which poxviruses must overcome to productively infect host cells. To inhibit PKR, many poxviruses encode a pseudosubstrate mimic of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2), designated K3 in vaccinia virus. Although the interaction between PKR and eIF2α is highly conserved, some K3 orthologs from host-restricted poxviruses were previously shown to inhibit PKR in a species-specific manner. To better define this host range function, we compared the sensitivity of PKR from 17 mammals to inhibition by K3 orthologs from closely related orthopoxviruses, a genus with a generally broader host range. The K3 orthologs showed species-specific inhibition of PKR and exhibited three distinct inhibition profiles. In some cases, PKR from closely related species showed dramatic differences in their sensitivity to K3 orthologs. Vaccinia virus expressing the camelpox virus K3 ortholog replicated more than three orders of magnitude better in human and sheep cells than a virus expressing vaccinia virus K3, but both viruses replicated comparably well in cow cells. Strikingly, in site-directed mutagenesis experiments between the variola virus and camelpox virus K3 orthologs, we found that different amino acid combinations were necessary to mediate improved or diminished inhibition of PKR derived from different host species. Because there is likely a limited number of possible variations in PKR that affect K3-interactions but still maintain PKR/eIF2α interactions, it is possible that by chance PKR from some potential new hosts may be susceptible to K3-mediated inhibition from a virus it has never previously encountered. We conclude that neither the sensitivity of host proteins to virus inhibition nor the effectiveness of viral immune antagonists can be inferred from their phylogenetic relatedness but must be experimentally determined.
Indexed as
Identifiers
What OpenQuestion holds
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.