ArticlemBio2019
Stable Occupancy of the Crimean-Congo Hemorrhagic Fever Virus-Encoded Deubiquitinase Blocks Viral Infection.
Article in mBio, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 20 citations in OpenAlex.
- Conformational Dynamics of Viral Protease Precursors in Maturation, Inhibition, and Drug-Resistance Development.Viruses · 2026Review
- Structure-Guided Discovery and Biochemical Validation of Novel Small-Molecule Inhibitors Predicted to Target the CCHFV OTU Protease Y89-W99 Pocket.International journal of molecular sciences · 2026Article
- Nairobi sheep disease virus: an emerging threat with unresolved pathogenesis and zoonotic potential.Journal of virology · 2026Review
- Targeting Crimean-Congo hemorrhagic fever virus: computational and MD-driven discovery of Moringa oleifera peptides against the RdRp-embedded OTU protease.Scientific reports · 2026Article
- Characteristics of viral ovarian tumor domain protease from two emerging orthonairoviruses and identification of Yezo virus human infections in northeastern China as early as 2012.Journal of virology · 2025Article
- Review
- The Role of Nucleocapsid Protein (NP) in the Immunology of Crimean-Congo Hemorrhagic Fever Virus (CCHFV).Viruses · 2024Review
- Evaluation of two inoculation routes of an adenovirus-mediated viral protein inhibitor in a Crimean-Congo hemorrhagic fever mouse model.Virus research · 2024Article
- Crimean-Congo haemorrhagic fever (CCHF): present and future therapeutic armamentarium.Le infezioni in medicina · 2024Review
- Innate immune response against vector-borne bunyavirus infection and viral countermeasures.Frontiers in cellular and infection microbiology · 2024Review
- Crimean-Congo haemorrhagic fever virus.Nature reviews. Microbiology · 2023Review
- The Role of Deubiquitinases in Virus Replication and Host Innate Immune Response.Frontiers in microbiology · 2022Review
- Crimean-Congo Hemorrhagic Fever Virus: Current Advances and Future Prospects of Antiviral Strategies.Viruses · 2021Review
- HERC5 and the ISGylation Pathway: Critical Modulators of the Antiviral Immune Response.Viruses · 2021Review
- Review
- Flipping the substrate preference of Hazara virus ovarian tumour domain protease through structure-based mutagenesis.Acta crystallographica. Section D, Structural biology · 2020Article
- ISG15 overexpression compensates the defect of Crimean-Congo hemorrhagic fever virus polymerase bearing a protease-inactive ovarian tumor domain.PLoS neglected tropical diseases · 2020Article
- Independent inhibition of the polymerase and deubiquitinase activities of the Crimean-Congo Hemorrhagic Fever Virus full-length L-protein.PLoS neglected tropical diseases · 2020Article
- Fluorescent Crimean-Congo hemorrhagic fever virus illuminates tissue tropism patterns and identifies early mononuclear phagocytic cell targets in Ifnar-/- mice.PLoS pathogens · 2019Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) infection can result in a severe hemorrhagic syndrome for which there are no antiviral interventions available to date. Certain RNA viruses, such as CCHFV, encode cysteine proteases of the ovarian tumor (OTU) family that antagonize interferon (IFN) production by deconjugating ubiquitin (Ub). The OTU of CCHFV, a negative-strand RNA virus, is dispensable for replication of the viral genome, despite being part of the large viral RNA polymerase. Here, we show that mutations that prevent binding of the OTU to cellular ubiquitin are required for the generation of recombinant CCHFV containing a mutated catalytic cysteine. Similarly, the high-affinity binding of a synthetic ubiquitin variant (UbV-CC4) to CCHFV OTU strongly inhibits viral growth. UbV-CC4 inhibits CCHFV infection even in the absence of intact IFN signaling, suggesting that its antiviral activity is not due to blocking the OTU's immunosuppressive function. Instead, the prolonged occupancy of the OTU with UbV-CC4 directly targets viral replication by interfering with CCHFV RNA synthesis. Together, our data provide mechanistic details supporting the development of antivirals targeting viral OTUs.
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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.