ArticlePLoS pathogens2019
The herpes simplex virus host shutoff (vhs) RNase limits accumulation of double stranded RNA in infected cells: Evidence for accelerated decay of duplex RNA.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Article
- Recombinant Alphaherpesvirus Vectors in Veterinary Vaccinology: Platforms, Applications, and Translational Challenges.International journal of molecular sciences · 2026Review
- Perturbation of RNA homeostasis impairs mitochondrial respiration during poxvirus infection through excess RNA accumulation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Dogcatcher2: Improved statistical detection of transcriptional readthrough and repetitive element analysis across sequencing platforms.bioRxiv : the preprint server for biology · 2026Article
- Universal and quantitative detection of double-stranded RNAs as a signature of pan-virus infections using a luciferase-based biosensor.Journal of biological engineering · 2025Article
- ADAR1 p150 prevents HSV-1 from triggering PKR/eIF2α-mediated translational arrest and is required for efficient viral replication.PLoS pathogens · 2025Article
- Long-read transcriptomics of caviid gammaherpesvirus 1: compiling a comprehensive RNA atlas.mSystems · 2025Article
- Pseudorabies Virus UL41 Hijacks IFN Response via JAK/STAT Pathway While Cellular TRIM21 Blocks it Through K48 Ubiquitination.Transboundary and emerging diseases · 2025Article
- Long-read Transcriptomics of Caviid Gammaherpesvirus 1: Compiling a Comprehensive RNA Atlas.bioRxiv : the preprint server for biology · 2024Article
- Translational arrest and mRNA decay are independent activities of alphaherpesvirus virion host shutoff proteins.The Journal of general virology · 2024Article
- RNA recognition by PKR during DNA virus infection.Journal of medical virology · 2024Review
- CCR4-NOT differentially controls host versus virus poly(a)-tail length and regulates HCMV infection.EMBO reports · 2023Article
- The Role of Viral RNA Degrading Factors in Shutoff of Host Gene Expression.Annual review of virology · 2022Review
- Herpes Simplex Virus 1 Expressing GFP-Tagged Virion Host Shutoff (vhs) Protein Uncouples the Activities of RNA Degradation and Differential Nuclear Retention of the Virus Transcriptome.Journal of virology · 2022Article
- Duck plague virus UL41 protein inhibits RIG-I/MDA5-mediated duck IFN-β production via mRNA degradation activity.Veterinary research · 2022Article
- Adenovirus prevents dsRNA formation by promoting efficient splicing of viral RNA.Nucleic acids research · 2022Article
- Minding the message: tactics controlling RNA decay, modification, and translation in virus-infected cells.Genes & development · 2022Review
- Widespread remodeling of the mProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Coronavirus Endoribonuclease Ensures Efficient Viral Replication and Prevents Protein Kinase R Activation.Journal of virology · 2021Article
- Time-course profiling of bovine alphaherpesvirus 1.1 transcriptome using multiplatform sequencing.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The herpes simplex virus virion host shutoff (vhs) RNase destabilizes cellular and viral mRNAs and blunts host innate antiviral responses. Previous work demonstrated that cells infected with vhs mutants display enhanced activation of the host double-stranded RNA (dsRNA)-activated protein kinase R (PKR), implying that vhs limits dsRNA accumulation in infected cells. Confirming this hypothesis, we show that partially complementary transcripts of the UL23/UL24 and UL30/31 regions of the viral genome increase in abundance when vhs is inactivated, giving rise to greatly increased levels of intracellular dsRNA formed by annealing of the overlapping portions of these RNAs. Thus, vhs limits accumulation of dsRNA at least in part by reducing the levels of complementary viral transcripts. We then asked if vhs also destabilizes dsRNA after its initial formation. Here, we used a reporter system employing two mCherry expression plasmids bearing complementary 3' UTRs to produce defined dsRNA species in uninfected cells. The dsRNAs are unstable, but are markedly stabilized by co-expressing the HSV dsRNA-binding protein US11. Strikingly, vhs delivered by super-infecting HSV virions accelerates the decay of these pre-formed dsRNAs in both the presence and absence of US11, a novel and unanticipated activity of vhs. Vhs binds the host RNA helicase eIF4A, and we find that vhs-induced dsRNA decay is attenuated by the eIF4A inhibitor hippuristanol, providing evidence that eIF4A participates in the process. Our results show that a herpesvirus host shutoff RNase destabilizes dsRNA in addition to targeting partially complementary viral mRNAs, raising the possibility that the mRNA destabilizing proteins of other viral pathogens dampen the host response to dsRNA through similar mechanisms.
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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.