ArticlePLoS pathogens2016
Fine-Tuning of the Kaposi's Sarcoma-Associated Herpesvirus Life Cycle in Neighboring Cells through the RTA-JAG1-Notch Pathway.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 31 citations in OpenAlex.
- KSHV hijacks the antiviral kinase IKKε to initiate lytic replication.PLoS pathogens · 2025Article
- Methylation of KSHV vCyclin by PRMT5 contributes to cell cycle progression and cell proliferation.PLoS pathogens · 2024Article
- The cellular Notch1 protein promotes KSHV reactivation in an Rta-dependent manner.Journal of virology · 2024Article
- A distinct isoform of lymphoid enhancer binding factor 1 (LEF1) epigenetically restricts EBV reactivation to maintain viral latency.PLoS pathogens · 2023Article
- The SUMO E3 ligase activity of ORF45 determines KSHV lytic replication.PLoS pathogens · 2022Article
- RSK1 SUMOylation is required for KSHV lytic replication.PLoS pathogens · 2021Article
- Kaposi's sarcoma-associated herpesvirus infection promotes proliferation of SH-SY5Y cells by the Notch signaling pathway.Cancer cell international · 2021Article
- Kaposi's Sarcoma-associated Herpesvirus microRNA mutants modulate cancer hallmark phenotypic differences in human endothelial cells.Journal of virology · 2021Article
- When Viruses Cross Developmental Pathways.Frontiers in cell and developmental biology · 2021Review
- Regulation of KSHV Latency and Lytic Reactivation.Viruses · 2020Review
- Lytic Induction Therapy against Epstein-Barr Virus-Associated Malignancies: Past, Present, and Future.Cancers · 2020Review
- Whitefly HES1 binds to the intergenic region of Tomato yellow leaf curl China virus and promotes viral gene transcription.Virology · 2020Article
- Article
- Genome-Wide Identification of Direct RTA Targets Reveals Key Host Factors for Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation.Journal of virology · 2019Article
- Upregulation of MicroRNA 711 Mediates HIV-1 Vpr Promotion of Kaposi's Sarcoma-Associated Herpesvirus Latency and Induction of Pro-proliferation and Pro-survival Cytokines by Targeting the Notch/NF-κB-Signaling Axis.Journal of virology · 2018Article
- The crystal structure of KSHV ORF57 reveals dimeric active sites important for protein stability and function.PLoS pathogens · 2018Article
- Transactivation of human endogenous retrovirus K (HERV-K) by KSHV promotes Kaposi's sarcoma development.Oncogene · 2018Article
- Antitumor activity of Notch‑1 inhibition in human colorectal carcinoma cells.Oncology reports · 2018Article
- Viral Oncology: Molecular Biology and Pathogenesis.Journal of clinical medicine · 2017Review
- KSHV and the Role of Notch Receptor Dysregulation in Disease Progression.Pathogens (Basel, Switzerland) · 2017Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is an oncogenic pathogen that displays latent and lytic life cycles. In KS lesions, infiltrated immune cells, secreted viral and/or cellular cytokines, and hypoxia orchestrate a chronic pro-lytic microenvironment that can promote KSHV reactivation. However, only a small subset of viruses spontaneously undergoes lytic replication in this pro-lytic microenvironment while the majority remains in latency. Here, we show that the expression of the Notch ligand JAG1 is induced by KSHV-encoded replication and transcription activator (RTA) during reactivation. JAG1 up-regulation activates Notch signaling in neighboring cells and prevents viral lytic replication. The suppression of JAG1 and Notch1 with inhibitors or small interfering RNA promotes lytic replication in the presence of RTA induction or under conditions of hypoxia. The underlying mechanism involves the Notch downstream effector hairy and enhancer of split 1 (Hes1), which directly binds lytic gene promoters and attenuates viral lytic gene expression. RTA interacts with lymphoid enhancer-binding factor 1 (LEF1), disrupts LEF1/Groucho/TLE suppressive complexes and releases LEF1 to activate JAG1 expression. Taken together, our results suggest that cells with viral lytic replication can inhibit KSHV reactivation in neighboring cells through an RTA-JAG1-Notch pathway. These data provide insight into the mechanism by which the virus maintains the balance between lytic and latent infection in the pro-lytic tumor microenvironment.
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