ArticleProceedings of the National Academy of Sciences of the United States of America2016
Myxoma virus M156 is a specific inhibitor of rabbit PKR but contains a loss-of-function mutation in Australian virus isolates.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 63 citations in OpenAlex.
- Systematic screen of PKR reveals genetic variants that broadly evade divergent viral pseudosubstrate inhibitors.bioRxiv : the preprint server for biology · 2026Article
- APOBEC3-driven attenuation of the 2022 global outbreak monkeypox virus relative to its clade IIb ancestor.Nature communications · 2026Article
- Molecular Determinants of Species-Specific Interactions Between Protein Kinase R and Poxvirus K3 Orthologs.Viruses · 2025Article
- The Role of Myxoma Virus Immune Modulators and Host Range Factors in Pathogenesis and Species Leaping.Viruses · 2025Review
- Poxvirus K3 Orthologs Regulate NF-κB-Dependent Inflammatory Responses by Targeting the PKR-eIF2α Axis in Multiple Species.Vaccines · 2025Article
- Protein Kinase R (PKR) as a Novel dsRNA Sensor in Antiviral Innate Immunity.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Host species-specific activity of the poxvirus PKR inhibitors E3 and K3 mediate host range function.Journal of virology · 2024Article
- Article
- 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
- Tanapox Virus and Yaba Monkey Tumor Virus K3 Orthologs Inhibit Primate Protein Kinase R in a Species-Specific Fashion.Viruses · 2024Article
- Cross-species transmission and host range genes in poxviruses.Virologica Sinica · 2024Review
- Article
- Systematic characterization of the local evolutionary space available to human PKR and vaccinia virus K3.bioRxiv : the preprint server for biology · 2023Article
- Molecular Mechanisms of Poxvirus Evolution.mBio · 2023Review
- Adaptive duplication and genetic diversification of protein kinase R contribute to the specificity of bat-virus interactions.Science advances · 2022Article
- Viral evasion of PKR restriction by reprogramming cellular stress granules.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Crocodilepox Virus Protein 157 Is an Independently Evolved Inhibitor of Protein Kinase R.Viruses · 2022Article
- 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
- Understanding the research advances on lumpy skin disease: A comprehensive literature review of experimental evidence.Frontiers in microbiology · 2022Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Myxoma virus (MYXV) is a rabbit-specific poxvirus, which is highly virulent in European rabbits. The attenuation of MYXV and the increased resistance of rabbits following the release of MYXV in Australia is one of the best-documented examples of host-pathogen coevolution. To elucidate the molecular mechanisms that contribute to the restriction of MYXV infection to rabbits and MYXV attenuation in the field, we have studied the interaction of the MYXV protein M156 with the host antiviral protein kinase R (PKR). In yeast and cell-culture transfection assays, M156 only inhibited rabbit PKR but not PKR from other tested mammalian species. Infection assays with human HeLa PKR knock-down cells, which were stably transfected with human or rabbit PKR, revealed that only human but not rabbit PKR was able to restrict MYXV infection, whereas both PKRs were able to restrict replication of a vaccinia virus (VACV) strain that lacks the PKR inhibitors E3 and K3. Inactivation of M156R led to MYXV virus attenuation in rabbit cells, which was rescued by the ectopic expression of VACV E3 and K3. We further show that a mutation in the M156 encoding gene that was identified in more than 50% of MYXV field isolates from Australia resulted in an M156 variant that lost its ability to inhibit rabbit PKR and led to virus attenuation. The species-specific inhibition of rabbit PKR by M156 and the M156 loss-of-function in Australian MYXV field isolates might thus contribute to the species specificity of MYXV and to the attenuation in the field, respectively.
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