ArticlePLoS pathogens2010
Upregulation of xCT by KSHV-encoded microRNAs facilitates KSHV dissemination and persistence in an environment of oxidative stress.
Article in PLoS pathogens, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 115 citations in OpenAlex.
- Systemically circulating viral and tumor-derived microRNAs in KSHV-associated malignancies.PLoS pathogens · 2013Trial
- Metabolomic Analysis of Lytic KSHV Infection: Induced Host Nucleotide Metabolism Is Required for Infectious Virus Production.Viruses · 2026Article
- The critical role of ferroptosis in virus-associated hematologic malignancies and its potential value in antiviral-antitumor therapy.Virulence · 2025Review
- Identification of RP-54745, an IL-1 Inhibitor Displaying Anticancer Activities for KSHV-Related Primary Effusion Lymphoma.Journal of medical virology · 2025Article
- Review
- Infection of human induced pluripotent stem cells by an oncogenic herpesvirus.Frontiers in cellular and infection microbiology · 2025Article
- Understanding Metabolic Pathway Rewiring by Oncogenic Gamma Herpesvirus.Journal of microbiology and biotechnology · 2024Review
- Molecular Mechanisms of Kaposi Sarcoma-Associated Herpesvirus (HHV8)-Related Lymphomagenesis.Cancers · 2024Review
- HPV16 integration regulates ferroptosis resistance via the c-Myc/miR-142-5p/HOXA5/SLC7A11 axis during cervical carcinogenesis.Cell & bioscience · 2024Article
- KSHV vIL-6 promotes SIRT3-induced deacetylation of SERBP1 to inhibit ferroptosis and enhance cellular transformation by inducing lipoyltransferase 2 mRNA degradation.PLoS pathogens · 2024Article
- Role of lymphatic endothelium specific hyaluronan receptor 1 in virus infection and associated diseases.Journal of medical virology · 2024Review
- Critical involvement of circular RNAs in virus-associated cancers.Genes & diseases · 2023Review
- Role of Histamine and Related Signaling in Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis and Oncogenesis.Viruses · 2023Article
- Review
- Picornavirus infection enhances aspartate by the SLC38A8 transporter to promote viral replication.PLoS pathogens · 2023Article
- Emerging role of miRNAs in the regulation of ferroptosis.Frontiers in molecular biosciences · 2023Review
- A major role for Nrf2 transcription factors in cell transformation by KSHV encoded oncogenes.Frontiers in oncology · 2022Article
- Human herpesvirus-encoded MicroRNA in host-pathogen interaction.Advances in biological regulation · 2021Review
- Metabolic reprogramming and metabolic sensors in KSHV-induced cancers and KSHV infection.Cell & bioscience · 2021Review
- xCT/SLC7A11 antiporter function inhibits HIV-1 infection.Virology · 2021Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Upregulation of xCT, the inducible subunit of a membrane-bound amino acid transporter, replenishes intracellular glutathione stores to maintain cell viability in an environment of oxidative stress. xCT also serves as a fusion-entry receptor for the Kaposi's sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi's sarcoma (KS). Ongoing KSHV replication and infection of new cell targets is important for KS progression, but whether xCT regulation within the tumor microenvironment plays a role in KS pathogenesis has not been determined. Using gene transfer and whole virus infection experiments, we found that KSHV-encoded microRNAs (KSHV miRNAs) upregulate xCT expression by macrophages and endothelial cells, largely through miR-K12-11 suppression of BACH-1-a negative regulator of transcription recognizing antioxidant response elements within gene promoters. Correlative functional studies reveal that upregulation of xCT by KSHV miRNAs increases cell permissiveness for KSHV infection and protects infected cells from death induced by reactive nitrogen species (RNS). Interestingly, KSHV miRNAs simultaneously upregulate macrophage secretion of RNS, and biochemical inhibition of RNS secretion by macrophages significantly reduces their permissiveness for KSHV infection. The clinical relevance of these findings is supported by our demonstration of increased xCT expression within more advanced human KS tumors containing a larger number of KSHV-infected cells. Collectively, these data support a role for KSHV itself in promoting de novo KSHV infection and the survival of KSHV-infected, RNS-secreting cells in the tumor microenvironment through the induction of xCT.
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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.