Integrin αvβ5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral Therapy
Summary: We perform a CRISPR-Cas9 genome-wide screen in glioblastoma stem cells and identify integrin αvβ5 as an internalization factor for Zika virus (ZIKV). Expression of αvβ5 is correlated with ZIKV susceptibility in various cells and tropism in developing human cerebral cortex. A blocking antibo...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719314913 |
| _version_ | 1811204749137018880 |
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| author | Shaobo Wang Qiong Zhang Shashi Kant Tiwari Gianluigi Lichinchi Edwin H. Yau Hui Hui Wanyu Li Frank Furnari Tariq M. Rana |
| author_facet | Shaobo Wang Qiong Zhang Shashi Kant Tiwari Gianluigi Lichinchi Edwin H. Yau Hui Hui Wanyu Li Frank Furnari Tariq M. Rana |
| author_sort | Shaobo Wang |
| collection | DOAJ |
| description | Summary: We perform a CRISPR-Cas9 genome-wide screen in glioblastoma stem cells and identify integrin αvβ5 as an internalization factor for Zika virus (ZIKV). Expression of αvβ5 is correlated with ZIKV susceptibility in various cells and tropism in developing human cerebral cortex. A blocking antibody against integrin αvβ5, but not αvβ3, efficiently inhibits ZIKV infection. ZIKV binds to cells but fails to internalize when treated with integrin αvβ5-blocking antibody. αvβ5 directly binds to ZIKV virions and activates focal adhesion kinase, which is required for ZIKV infection. Finally, αvβ5 blocking antibody or two inhibitors, SB273005 and cilengitide, reduces ZIKV infection and alleviates ZIKV-induced pathology in human neural stem cells and in mouse brain. Altogether, our findings identify integrin αvβ5 as an internalization factor for ZIKV, providing a promising therapeutic target, as well as two drug candidates for prophylactic use or treatments for ZIKV infections. : Wang et al. show that Zika virus (ZIKV) uses integrin αvβ5 to infect neural stem cells. ZIKV infection can be inhibited by αvβ5 blocking antibody or inhibitors, SB273005 and cilengitide, in human neural stem cells and in mouse brain, providing drug candidates for prophylactic use or treatments for ZIKV infections. Keywords: ZIKV internalization, integrin, neurotropism, CRISPR, stem cells, Cilengitide, SB273005, glioblastoma, Zika treatment |
| first_indexed | 2024-04-12T03:18:56Z |
| format | Article |
| id | doaj.art-c19b50daadf84ea7bf4bef334925960c |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T03:18:56Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-c19b50daadf84ea7bf4bef334925960c2022-12-22T03:49:59ZengElsevierCell Reports2211-12472020-01-01304969983.e4Integrin αvβ5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral TherapyShaobo Wang0Qiong Zhang1Shashi Kant Tiwari2Gianluigi Lichinchi3Edwin H. Yau4Hui Hui5Wanyu Li6Frank Furnari7Tariq M. Rana8Division of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USADivision of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USADivision of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USADivision of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USADivision of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Division of Hematology-Oncology, Department of Internal Medicine, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USADivision of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Department of Biology, Bioinformatics Program, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USADivision of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Department of Biology, Bioinformatics Program, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USALudwig Institute for Cancer Research, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA; Department of Pathology, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USADivision of Genetics, Department of Pediatrics, Institute for Genomic Medicine, Program in Immunology, University of California San Diego School of Medicine, 9500 Gilman Drive MC 0762, La Jolla, CA 92093, USA; Department of Biology, Bioinformatics Program, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA; Moores Cancer Center, University of California San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093, USA; Corresponding authorSummary: We perform a CRISPR-Cas9 genome-wide screen in glioblastoma stem cells and identify integrin αvβ5 as an internalization factor for Zika virus (ZIKV). Expression of αvβ5 is correlated with ZIKV susceptibility in various cells and tropism in developing human cerebral cortex. A blocking antibody against integrin αvβ5, but not αvβ3, efficiently inhibits ZIKV infection. ZIKV binds to cells but fails to internalize when treated with integrin αvβ5-blocking antibody. αvβ5 directly binds to ZIKV virions and activates focal adhesion kinase, which is required for ZIKV infection. Finally, αvβ5 blocking antibody or two inhibitors, SB273005 and cilengitide, reduces ZIKV infection and alleviates ZIKV-induced pathology in human neural stem cells and in mouse brain. Altogether, our findings identify integrin αvβ5 as an internalization factor for ZIKV, providing a promising therapeutic target, as well as two drug candidates for prophylactic use or treatments for ZIKV infections. : Wang et al. show that Zika virus (ZIKV) uses integrin αvβ5 to infect neural stem cells. ZIKV infection can be inhibited by αvβ5 blocking antibody or inhibitors, SB273005 and cilengitide, in human neural stem cells and in mouse brain, providing drug candidates for prophylactic use or treatments for ZIKV infections. Keywords: ZIKV internalization, integrin, neurotropism, CRISPR, stem cells, Cilengitide, SB273005, glioblastoma, Zika treatmenthttp://www.sciencedirect.com/science/article/pii/S2211124719314913 |
| spellingShingle | Shaobo Wang Qiong Zhang Shashi Kant Tiwari Gianluigi Lichinchi Edwin H. Yau Hui Hui Wanyu Li Frank Furnari Tariq M. Rana Integrin αvβ5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral Therapy Cell Reports |
| title | Integrin αvβ5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral Therapy |
| title_full | Integrin αvβ5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral Therapy |
| title_fullStr | Integrin αvβ5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral Therapy |
| title_full_unstemmed | Integrin αvβ5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral Therapy |
| title_short | Integrin αvβ5 Internalizes Zika Virus during Neural Stem Cells Infection and Provides a Promising Target for Antiviral Therapy |
| title_sort | integrin αvβ5 internalizes zika virus during neural stem cells infection and provides a promising target for antiviral therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719314913 |
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