ArticlePloS one2014
Sphingosine kinase-2 maintains viral latency and survival for KSHV-infected endothelial cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02229981 (An Early-Phase Clinical Trial Evaluating ABC294640 in Patients With Refractory/Relapsed Diffuse Large B-cell Lymphoma or Kaposi Sarcoma), which is not on this 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.
An Early-Phase Clinical Trial Evaluating ABC294640 in Patients With Refractory/Relapsed Diffuse Large B-cell Lymphoma or Kaposi Sarcoma
Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Enzymatic independent role of sphingosine kinase 2 in regulating the expression of type I interferon during influenza A virus infection.PLoS pathogens · 2022Article
- Loss of sphingosine kinase 2 protects against cisplatin-induced kidney injury.American journal of physiology. Renal physiology · 2022Article
- Article
- Potential drug development and therapeutic approaches for clinical intervention in COVID-19.Bioorganic chemistry · 2021Review
- Sphingosine kinase 2 restricts T cell immunopathology but permits viral persistence.The Journal of clinical investigation · 2020Article
- Repurposing anticancer drugs for the management of COVID-19.European journal of cancer (Oxford, England : 1990) · 2020Review
- Article
- SARS-CoV-2 Infection: A Role for S1P/S1P Receptor Signaling in the Nervous System?International journal of molecular sciences · 2020Article
- Emerging Connections of S1P-Metabolizing Enzymes with Host Defense and Immunity During Virus Infections.Viruses · 2019Review
- Ceramide Suppresses Influenza A Virus ReplicationJournal of virology · 2019Article
- Transient inhibition of sphingosine kinases confers protection to influenza A virus infected mice.Antiviral research · 2018Article
- ABC294640, A Novel Sphingosine Kinase 2 Inhibitor, Induces Oncogenic Virus-Infected Cell Autophagic Death and Represses Tumor Growth.Molecular cancer therapeutics · 2017Article
- Lipids, lipid metabolism and Kaposi's sarcoma-associated herpesvirus pathogenesis.Virologica Sinica · 2017Review
- An In Vitro Model for Studying Cellular Transformation by Kaposi Sarcoma Herpesvirus.Journal of visualized experiments : JoVE · 2017Article
- Up-regulation of tumor suppressor genes by exogenous dhC16-Cer contributes to its anti-cancer activity in primary effusion lymphoma.Oncotarget · 2017Article
- Transcriptomic analysis of KSHV-infected primary oral fibroblasts: The role of interferon-induced genes in the latency of oncogenic virus.Oncotarget · 2016Article
- Article
- Sphingosine kinase 2 is a chikungunya virus host factor co-localized with the viral replication complex.Emerging microbes & infections · 2015Article
- Ceramides promote apoptosis for virus-infected lymphoma cells through induction of ceramide synthases and viral lytic gene expression.Oncotarget · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Phosphorylation of sphingosine by sphingosine kinases (SphK1 and SphK2) generates sphingosine-1-phosphate (S1P), a bioactive sphingolipid which promotes cancer cell survival and tumor progression in vivo. We have recently reported that targeting SphK2 induces apoptosis for human primary effusion lymphoma (PEL) cell lines infected by the Kaposi's sarcoma-associated herpesvirus (KSHV), and this occurs in part through inhibition of canonical NF-κB activation. In contrast, pharmacologic inhibition of SphK2 has minimal impact for uninfected B-cell lines or circulating human B cells from healthy donors. Therefore, we designed additional studies employing primary human endothelial cells to explore mechanisms responsible for the selective death observed for KSHV-infected cells during SphK2 targeting. Using RNA interference and a clinically relevant pharmacologic approach, we have found that targeting SphK2 induces apoptosis selectively for KSHV-infected endothelial cells through induction of viral lytic gene expression. Moreover, this effect occurs through repression of KSHV-microRNAs regulating viral latency and signal transduction, including miR-K12-1 which targets IκBα to facilitate activation of NF-κB, and ectopic expression of miR-K12-1 restores NF-κB activation and viability for KSHV-infected endothelial cells during SphK2 inhibition. These data illuminate a novel survival mechanism and potential therapeutic target for KSHV-infected endothelial cells: SphK2-associated maintenance of viral latency.
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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.