ArticlePLoS pathogens2019
Identification of new antiviral agents against Kaposi's sarcoma-associated herpesvirus (KSHV) by high-throughput drug screening reveals the role of histamine-related signaling in promoting viral lytic reactivation.
Article in PLoS pathogens, 2019. 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, 33 citations in OpenAlex.
- miR-26a-5p Activates Antiviral Innate Immunity via Direct Binding and Activation of RIG-I.Viruses · 2026Article
- Disrupting the OTUD4-USP7 deubiquitinase complex to suppress herpesvirus replication: a novel antiviral strategy.PLoS pathogens · 2025Article
- Infectious etiologies of conjunctival tumors.Expert review of ophthalmology · 2025Article
- Microneedle-Array-Mediated Transdermal Delivery of GCV-Functionalized Zeolitic Imidazolate Framework-8 Nanoparticles for KSHV Treatment.International journal of molecular sciences · 2024Article
- In Silico Drug Repurposing Uncovered the Antiviral Potential of the Antiparasitic Drug Oxibendazole Against the Chikungunya Virus.ACS omega · 2024Article
- Folate-Targeted Nanocarriers Co-Deliver Ganciclovir and miR-34a-5p for Combined Anti-KSHV Therapy.International journal of molecular sciences · 2024Article
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.PLoS pathogens · 2023Article
- Role of Histamine and Related Signaling in Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis and Oncogenesis.Viruses · 2023Article
- Polypharmacology-based kinome screen identifies new regulators of KSHV reactivation.bioRxiv : the preprint server for biology · 2023Article
- Targeting Kaposi's sarcoma associated herpesvirus encoded protease (ORF17) by a lysophosphatidic acid molecule for treating KSHV associated diseases.Frontiers in cell and developmental biology · 2023Article
- Oncolytic strategy using new bifunctional HDACs/BRD4 inhibitors against virus-associated lymphomas.PLoS pathogens · 2023Article
- Unboxing the molecular modalities of mutagens in cancer.Environmental science and pollution research international · 2022Review
- Kaposi Sarcoma, a Trifecta of Pathogenic Mechanisms.Diagnostics (Basel, Switzerland) · 2022Review
- The regulation of KSHV lytic reactivation by viral and cellular factors.Current opinion in virology · 2022Review
- Activation of IL1 signaling molecules by Kaposi's sarcoma-associated herpesvirus.Frontiers in cellular and infection microbiology · 2022Article
- 3D culture conditions support Kaposi's sarcoma herpesvirus (KSHV) maintenance and viral spread in endothelial cells.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Spotlight on ocular Kaposi's sarcoma: an update on the presentation, diagnosis, and management options.Expert review of ophthalmology · 2021Article
- Endoplasmic Reticulum-Shaping Atlastin Proteins Facilitate KSHV Replication.Frontiers in cellular and infection microbiology · 2021Article
- Regulation of KSHV Latency and Lytic Reactivation.Viruses · 2020Review
- Cells of the Innate and Adaptive Immune Systems in Kaposi's Sarcoma.Journal of immunology research · 2020Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Kaposi's sarcoma-associated herpesvirus (KSHV) causes several human cancers, such as Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). Current treatment options for KSHV infection and virus associated diseases are sometimes ineffective, therefore, more effectively antiviral agents are urgently needed. As a herpesvirus, lytic replication is critical for KSHV pathogenesis and oncogenesis. In this study, we have established a high-throughput screening assay by using an inducible KSHV+ cell-line, iSLK.219. After screening a compound library that consisted of 1280 Food and Drug Administration (FDA)-approved drugs, 15 hit compounds that effectively inhibited KSHV virion production were identified, most of which have never been reported with anti-KSHV activities. Interestingly, 3 of these drugs target histamine receptors or signaling. Our data further confirmed that antagonists targeting different histamine receptors (HxRs) displayed excellent inhibitory effects on KSHV lytic replication from induced iSLK.219 or BCBL-1 cells. In contrast, histamine and specific agonists of HxRs promoted viral lytic replication from induced iSLK.219 or KSHV-infected primary cells. Mechanistic studies indicated that downstream MAPK and PI3K/Akt signaling pathways were required for histamine/receptors mediated promotion of KSHV lytic replication. Direct knockdown of HxRs in iSLK.219 cells effectively blocked viral lytic gene expression during induction. Using samples from a cohort of HIV+ patients, we found that the KSHV+ group has much higher levels of histamine in their plasma and saliva than the KSHV- group. Taken together, our data have identified new anti-KSHV agents and provided novel insights into the molecular bases of host factors that contribute to lytic replication and reactivation of this oncogenic herpesvirus.
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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.