ArticleJournal of virology2012
Species specificity of protein kinase r antagonism by cytomegalovirus TRS1 genes.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
What it found
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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.
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.
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Who cites it
23 citing papers in PubMed, 25 citations in OpenAlex.
- Viral interferon antagonism shapes host tropism.PLoS pathogens · 2025Review
- Antagonism of Protein Kinase R by Large DNA Viruses.Pathogens (Basel, Switzerland) · 2022Review
- Gene amplification acts as a molecular foothold to facilitate cross-species adaptation and evasion of multiple antiviral pathways.Virus evolution · 2022Article
- Rapid adaptation to human protein kinase R by a unique genomic rearrangement in rhesus cytomegalovirus.PLoS pathogens · 2021Article
- Evolution and Genetic Diversity of Primate Cytomegaloviruses.Microorganisms · 2020Review
- Species-Specific Host-Virus Interactions: Implications for Viral Host Range and Virulence.Trends in microbiology · 2020Review
- 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
- Species-specific functions of Epstein-Barr virus nuclear antigen 2 (EBNA2) reveal dual roles for initiation and maintenance of B cell immortalization.PLoS pathogens · 2017Article
- KSHV inhibits stress granule formation by viral ORF57 blocking PKR activation.PLoS pathogens · 2017Article
- A Single Amino Acid Dictates Protein Kinase R Susceptibility to Unrelated Viral Antagonists.PLoS pathogens · 2016Article
- Human Cytomegalovirus pTRS1 and pIRS1 Antagonize Protein Kinase R To Facilitate Virus Replication.Journal of virology · 2016Article
- Essential role of protein kinase R antagonism by TRS1 in human cytomegalovirus replication.Virology · 2016Article
- An Evolutionary View of the Arms Race between Protein Kinase R and Large DNA Viruses.Journal of virology · 2016Review
- On the relative roles of background selection and genetic hitchhiking in shaping human cytomegalovirus genetic diversity.Molecular ecology · 2016Article
- Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins.Autophagy · 2016Article
- Experimental Evolution Identifies Vaccinia Virus Mutations in A24R and A35R That Antagonize the Protein Kinase R Pathway and Accompany Collapse of an Extragenic Gene Amplification.Journal of virology · 2015Article
- Adaptive gene amplification as an intermediate step in the expansion of virus host range.PLoS pathogens · 2014Article
- Functional annotation of human cytomegalovirus gene products: an update.Frontiers in microbiology · 2014Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The host antiviral protein kinase R (PKR) has rapidly evolved during primate evolution, likely in response to challenges posed by many different viral antagonists, such as the TRS1 gene of cytomegaloviruses (CMVs). In turn, viral antagonists have adapted to changes in PKR. As a result of this "arms race," modern TRS1 alleles in CMVs may function differently in cells derived from alternative species. We have previously shown that human CMV TRS1 (HuTRS1) blocks the PKR pathway and rescues replication of a vaccinia virus mutant lacking its major PKR antagonist in human cells. We now demonstrate that HuTRS1 does not have these activities in Old World monkey cells. Conversely, the rhesus cytomegalovirus homologue of HuTRS1 (RhTRS1) fulfills these functions in African green monkey cells, but not rhesus or human cells. Both TRS1 proteins bind to double-stranded RNA and, in the cell types in which they can rescue VVΔE3L replication, they also bind to PKR and prevent phosphorylation of the α-subunit of eukaryotic initiation factor 2. However, while HuTRS1 binds to inactive human PKR and prevents its autophosphorylation, RhTRS1 binds to phosphorylated African green monkey PKR. These studies reveal that evolutionary adaptations in this critical host defense protein have altered its binding interface in a way that has resulted in a qualitatively altered mechanism of PKR antagonism by viral TRS1 alleles from different CMVs. These results suggest that PKR antagonism is likely one of the factors that contributes to species specificity of cytomegalovirus replication.
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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.