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Zika Virus Targets Glioblastoma Stem Cells through a SOX2-Integrin αvß5 Axis.
Zhu, Zhe; Mesci, Pinar; Bernatchez, Jean A; Gimple, Ryan C; Wang, Xiuxing; Schafer, Simon T; Wettersten, Hiromi I; Beck, Sungjun; Clark, Alex E; Wu, Qiulian; Prager, Briana C; Kim, Leo J Y; Dhanwani, Rekha; Sharma, Sonia; Garancher, Alexandra; Weis, Sara M; Mack, Stephen C; Negraes, Priscilla D; Trujillo, Cleber A; Penalva, Luiz O; Feng, Jing; Lan, Zhou; Zhang, Rong; Wessel, Alex W; Dhawan, Sanjay; Diamond, Michael S; Chen, Clark C; Wechsler-Reya, Robert J; Gage, Fred H; Hu, Hongzhen; Siqueira-Neto, Jair L; Muotri, Alysson R; Cheresh, David A; Rich, Jeremy N.
Afiliação
  • Zhu Z; Department of Medicine, Division of Regenerative Medicine, University of California School of Medicine, San Diego, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
  • Mesci P; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA; Department of Pediatrics, Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92307, USA; Department of Cellular and Molecular Medicine, Stem C
  • Bernatchez JA; Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92037, USA.
  • Gimple RC; Department of Medicine, Division of Regenerative Medicine, University of California School of Medicine, San Diego, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA; Case Western Reserve University Medical Scientist Trainin
  • Wang X; Department of Medicine, Division of Regenerative Medicine, University of California School of Medicine, San Diego, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
  • Schafer ST; Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Wettersten HI; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA; Department of Pathology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
  • Beck S; Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92037, USA.
  • Clark AE; Department of Cellular and Molecular Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92037, USA.
  • Wu Q; Department of Medicine, Division of Regenerative Medicine, University of California School of Medicine, San Diego, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA.
  • Prager BC; Department of Medicine, Division of Regenerative Medicine, University of California School of Medicine, San Diego, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA; Case Western Reserve University Medical Scientist Trainin
  • Kim LJY; Department of Medicine, Division of Regenerative Medicine, University of California School of Medicine, San Diego, La Jolla, CA 92037, USA; Case Western Reserve University Medical Scientist Training Program, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Department of
  • Dhanwani R; La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
  • Sharma S; La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA.
  • Garancher A; Tumor Initiation and Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Weis SM; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA; Department of Pathology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA.
  • Mack SC; Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston, TX 77030, USA.
  • Negraes PD; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA; Department of Pediatrics, Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92307, USA.
  • Trujillo CA; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA; Department of Pediatrics, Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92307, USA.
  • Penalva LO; Children's Cancer Research Institute - UTHSCSA, San Antonio, TX 78229, USA.
  • Feng J; Department of Anesthesiology, Center for the Study of Itch, Washington University School of Medicine in St. Louis, St. Louis, MO 63130, USA.
  • Lan Z; Department of Anesthesiology, Center for the Study of Itch, Washington University School of Medicine in St. Louis, St. Louis, MO 63130, USA.
  • Zhang R; Departments of Medicine, Molecular Microbiology, Pathology, and Immunology and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63130, USA.
  • Wessel AW; Departments of Medicine, Molecular Microbiology, Pathology, and Immunology and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63130, USA.
  • Dhawan S; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
  • Diamond MS; Departments of Medicine, Molecular Microbiology, Pathology, and Immunology and The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63130, USA.
  • Chen CC; Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA.
  • Wechsler-Reya RJ; Tumor Initiation and Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA.
  • Gage FH; Laboratory of Genetics, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
  • Hu H; Department of Anesthesiology, Center for the Study of Itch, Washington University School of Medicine in St. Louis, St. Louis, MO 63130, USA.
  • Siqueira-Neto JL; Department of Cellular and Molecular Medicine, Stem Cell Program, School of Medicine, University of California, San Diego, La Jolla, CA 92307, USA. Electronic address: jairlage@ucsd.edu.
  • Muotri AR; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA; Department of Pediatrics, Rady Children's Hospital San Diego, School of Medicine, University of California, San Diego, La Jolla, CA 92307, USA. Electronic address: muotri@ucsd.edu.
  • Cheresh DA; Department of Pathology, Moores Cancer Center, University of California, San Diego, La Jolla, CA 92037, USA. Electronic address: dcheresh@ucsd.edu.
  • Rich JN; Department of Medicine, Division of Regenerative Medicine, University of California School of Medicine, San Diego, La Jolla, CA 92037, USA; Sanford Consortium for Regenerative Medicine, 2880 Torrey Pines Scenic Drive, La Jolla, CA 92037, USA; Department of Neurosciences, University of California, Sa
Cell Stem Cell ; 26(2): 187-204.e10, 2020 02 06.
Article em En | MEDLINE | ID: mdl-31956038
ABSTRACT
Zika virus (ZIKV) causes microcephaly by killing neural precursor cells (NPCs) and other brain cells. ZIKV also displays therapeutic oncolytic activity against glioblastoma (GBM) stem cells (GSCs). Here we demonstrate that ZIKV preferentially infected and killed GSCs and stem-like cells in medulloblastoma and ependymoma in a SOX2-dependent manner. Targeting SOX2 severely attenuated ZIKV infection, in contrast to AXL. As mechanisms of SOX2-mediated ZIKV infection, we identified inverse expression of antiviral interferon response genes (ISGs) and positive correlation with integrin αv (ITGAV). ZIKV infection was disrupted by genetic targeting of ITGAV or its binding partner ITGB5 and by an antibody specific for integrin αvß5. ZIKV selectively eliminated GSCs from species-matched human mature cerebral organoids and GBM surgical specimens, which was reversed by integrin αvß5 inhibition. Collectively, our studies identify integrin αvß5 as a functional cancer stem cell marker essential for GBM maintenance and ZIKV infection, providing potential brain tumor therapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glioblastoma / Células-Tronco Neurais / Zika virus / Infecção por Zika virus Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Glioblastoma / Células-Tronco Neurais / Zika virus / Infecção por Zika virus Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article