ArticleProceedings of the National Academy of Sciences of the United States of America2013
Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 117 citations in OpenAlex.
- In vivo assessment of equine arteritis virus vaccine improvement by disabling the deubiquitinase activity of papain-like protease 2.Veterinary microbiology · 2015Trial
- Conserved structural features of RNA export pores spanning the double membrane of arterivirus and coronavirus replication organelles.Journal of virology · 2026Article
- Equine arteritis virus Nsp10 promotes MAVS proteasomal degradation via E3 ligases Smurf1/MARCH5.Journal of virology · 2026Article
- Venturing into host-pathogen interaction in Crimean-Congo hemorrhagic fever to highlight terra incognita.Frontiers in immunology · 2026Review
- DIG-DUBs: mechanisms and functions of ISG15 deconjugation by human and viral cross-reactive ubiquitin proteases.Biochemical Society transactions · 2025Article
- Mechanism, structural and functional insights into nidovirus-induced double-membrane vesicles.Frontiers in immunology · 2024Review
- ISG15: its roles in SARS-CoV-2 and other viral infections.Trends in microbiology · 2023Review
- Demonstrating the importance of porcine reproductive and respiratory syndrome virus papain-like protease 2 deubiquitinating activity in viral replication by structure-guided mutagenesis.PLoS pathogens · 2023Article
- Identification and classification of papain-like cysteine proteinases.The Journal of biological chemistry · 2023Article
- Engineering potent live attenuated coronavirus vaccines by targeted inactivation of the immune evasive viral deubiquitinase.Nature communications · 2023Article
- The alphavirus nonstructural protein 2 NTPase induces a host translational shut-off through phosphorylation of eEF2 via cAMP-PKA-eEF2K signaling.PLoS pathogens · 2023Article
- Reprogramming viral immune evasion for a rational design of next-generation vaccines for RNA viruses.Frontiers in immunology · 2023Review
- The US3 Kinase of Herpes Simplex Virus Phosphorylates the RNA Sensor RIG-I To Suppress Innate Immunity.Journal of virology · 2022Article
- Viral deubiquitinases and innate antiviral immune response in livestock and poultry.The Journal of veterinary medical science · 2022Review
- UCHL1 as a novel target in breast cancer: emerging insights from cell and chemical biology.British journal of cancer · 2022Review
- Evasion of interferon-mediated immune response by arteriviruses.Frontiers in immunology · 2022Review
- Papain-like protease of SARS-CoV-2 inhibits RLR signaling in a deubiquitination-dependent and deubiquitination-independent manner.Frontiers in immunology · 2022Article
- The Role of Deubiquitinases in Virus Replication and Host Innate Immune Response.Frontiers in microbiology · 2022Review
- The dual role of phytochemicals on SARS-CoV-2 inhibition by targeting host and viral proteins.Journal of traditional and complementary medicine · 2022Article
- Structure of the multiple functional domains from coronavirus nonstructural protein 3.Emerging microbes & infections · 2021Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein ubiquitination regulates important innate immune responses. The discovery of viruses encoding deubiquitinating enzymes (DUBs) suggests they remove ubiquitin to evade ubiquitin-dependent antiviral responses; however, this has never been conclusively demonstrated in virus-infected cells. Arteriviruses are economically important positive-stranded RNA viruses that encode an ovarian tumor (OTU) domain DUB known as papain-like protease 2 (PLP2). This enzyme is essential for arterivirus replication by cleaving a site within the viral replicase polyproteins and also removes ubiquitin from cellular proteins. To dissect this dual specificity, which relies on a single catalytic site, we determined the crystal structure of equine arteritis virus PLP2 in complex with ubiquitin (1.45 Å). PLP2 binds ubiquitin using a zinc finger that is uniquely integrated into an exceptionally compact OTU-domain fold that represents a new subclass of zinc-dependent OTU DUBs. Notably, the ubiquitin-binding surface is distant from the catalytic site, which allowed us to mutate this surface to significantly reduce DUB activity without affecting polyprotein cleavage. Viruses harboring such mutations exhibited WT replication kinetics, confirming that PLP2-mediated polyprotein cleavage was intact, but the loss of DUB activity strikingly enhanced innate immune signaling. Compared with WT virus infection, IFN-β mRNA levels in equine cells infected with PLP2 mutants were increased by nearly an order of magnitude. Our findings not only establish PLP2 DUB activity as a critical factor in arteriviral innate immune evasion, but the selective inactivation of DUB activity also opens unique possibilities for developing improved live attenuated vaccines against arteriviruses and other viruses encoding similar dual-specificity proteases.
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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.