ArticlePloS one2017
RNAi screen reveals a role of SPHK2 in dengue virus-mediated apoptosis in hepatic cell lines.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- Decoding dengue's neurological assault: insights from single-cell CNS analysis in an immunocompromised mouse model.Journal of neuroinflammation · 2025Article
- Antiviral activity of pimecrolimus against dengue virus type 2 infection in vitro and in vivo.Scientific reports · 2024Article
- Novel genetic regulators of fibrinogen synthesis identified by an in vitro experimental platform.Journal of thrombosis and haemostasis : JTH · 2023Article
- Arbovirus-vector protein interactomics identifies Loquacious as a co-factor for dengue virus replication in Aedes mosquitoes.PLoS pathogens · 2022Article
- Article
- Flaviviruses: Innate Immunity, Inflammasome Activation, Inflammatory Cell Death, and Cytokines.Frontiers in immunology · 2022Review
- Review
- The Dual Regulation of Apoptosis by Flavivirus.Frontiers in microbiology · 2021Review
- Zika M Oligopeptide ZAMP Confers Cell Death-Promoting Capability to a Soluble Tumor-Associated Antigen through Caspase-3/7 Activation.International journal of molecular sciences · 2020Article
- Crocetin Improves Dengue Virus-Induced Liver Injury.Viruses · 2020Article
- Suppression of µ1 subunit of the adaptor protein complex 2 reduces dengue virus release.Virus genes · 2020Article
- Emerging Connections of S1P-Metabolizing Enzymes with Host Defense and Immunity During Virus Infections.Viruses · 2019Review
- Role of MAPK/MNK1 signaling in virus replication.Virus research · 2018Review
- Divergent Role of Sphingosine 1-Phosphate in Liver Health and Disease.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatic dysfunction is a feature of dengue virus (DENV) infection. Hepatic biopsy specimens obtained from fatal cases of DENV infection show apoptosis, which relates to the pathogenesis of DENV infection. However, how DENV induced liver injury is not fully understood. In this study, we aim to identify the factors that influence cell death by employing an apoptosis-related siRNA library screening. Our results show the effect of 558 gene silencing on caspase 3-mediated apoptosis in DENV-infected Huh7 cells. The majority of genes that contributed to apoptosis were the apoptosis-related kinase enzymes. Tumor necrosis factor superfamily member 12 (TNFSF12), and sphingosine kinase 2 (SPHK2), were selected as the candidate genes to further validate their influences on DENV-induced apoptosis. Transfection of siRNA targeting SPHK2 but not TNFSF12 genes reduced apoptosis determined by Annexin V/PI staining. Knockdown of SPHK2 did not reduce caspase 8 activity; however, did significantly reduce caspase 9 activity, suggesting its involvement of SPHK2 in the intrinsic pathway of apoptosis. Treatment of ABC294649, an inhibitor of SPHK2, reduced the caspase 3 activity, suggesting the involvement of its kinase activity in apoptosis. Knockdown of SPHK2 significantly reduced caspase 3 activity not only in DENV-infected Huh7 cells but also in DENV-infected HepG2 cells. Our results were consistent across all of the four serotypes of DENV infection, which supports the pro-apoptotic role of SPHK2 in DENV-infected liver cells.
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