ArticleJournal of virology2020
Targeting Kaposi's Sarcoma-Associated Herpesvirus ORF21 Tyrosine Kinase and Viral Lytic Reactivation by Tyrosine Kinase Inhibitors Approved for Clinical Use.
Article in Journal of virology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- KSHV-infected endothelial cells expand and up-regulate angiogenic pathways and CXCR4 in patient-derived Kaposi sarcoma models.Science translational medicine · 2026Article
- Human oncogenic herpesvirus latency proteins activate NEK2 to promote chromosomal instability and tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Biological characterization and antibacterial effects of a novel virulentFrontiers in microbiology · 2025Article
- Mapping herpesvirus-driven impacts on the cellular milieu and transcriptional profile of Kaposi sarcoma in patient-derived mouse models.bioRxiv : the preprint server for biology · 2024Article
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.PLoS pathogens · 2023Article
- Mouse Models for Human Herpesviruses.Pathogens (Basel, Switzerland) · 2023Review
- The Kaposi's sarcoma progenitor enigma: KSHV-induced MEndT-EndMT axis.Trends in molecular medicine · 2023Review
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.bioRxiv : the preprint server for biology · 2023Article
- Kaposi's Sarcoma-Associated Herpesvirus ORF21 Enhances the Phosphorylation of MEK and the Infectivity of Progeny Virus.International journal of molecular sciences · 2023Article
- Kaposi Sarcoma, a Trifecta of Pathogenic Mechanisms.Diagnostics (Basel, Switzerland) · 2022Review
- Whole-genome sequencing of Kaposi sarcoma-associated herpesvirus (KSHV/HHV8) reveals evidence for two African lineages.Virology · 2022Article
- Review
- Recent Advances in Developing Treatments of Kaposi's Sarcoma Herpesvirus-Related Diseases.Viruses · 2021Review
- 3D culture conditions support Kaposi's sarcoma herpesvirus (KSHV) maintenance and viral spread in endothelial cells.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Manipulation of Focal Adhesion Signaling by Pathogenic Microbes.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) is the cause of three human malignancies: Kaposi's sarcoma, primary effusion lymphoma, and the plasma cell variant of multicentric Castleman disease. Previous research has shown that several cellular tyrosine kinases play crucial roles during several steps in the virus replication cycle. Two KSHV proteins also have protein kinase function: open reading frame (ORF) 36 encodes a serine-threonine kinase, while ORF21 encodes a thymidine kinase (TK), which has recently been found to be an efficient tyrosine kinase. In this study, we explore the role of the ORF21 tyrosine kinase function in KSHV lytic replication. By generating a recombinant KSHV mutant with an enzymatically inactive ORF21 protein, we show that the tyrosine kinase function of ORF21/TK is not required for the progression of the lytic replication in tissue culture but that it is essential for the phosphorylation and activation to toxic moieties of the antiviral drugs zidovudine and brivudine. In addition, we identify several tyrosine kinase inhibitors, already in clinical use against human malignancies, which potently inhibit not only ORF21 TK kinase function but also viral lytic reactivation and the development of KSHV-infected endothelial tumors in mice. Since they target both cellular tyrosine kinases and a viral kinase, some of these compounds might find a use in the treatment of KSHV-associated malignancies.
Indexed as
Identifiers
What OpenQuestion holds
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.