دورية أكاديمية
ARF6 is a host factor for SARS-CoV-2 infection in vitro .
| العنوان: | ARF6 is a host factor for SARS-CoV-2 infection in vitro . |
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| المؤلفون: | Mirabelli C; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA.; Present address: Institut für Virologie und Zellbiologie, University of Lübeck, Lübeck, Germany., Bragazzi Cunha J; Department of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, Michigan, USA., Wotring JW; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA., Sherman EJ; Department of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, Michigan, USA.; Present address: Territory Manager at Takara Bio, Inc., MI, MN, IN, KY, USA., El Saghir J; Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA., Harder J; Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA., Kretzler M; Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, Michigan, USA., Sexton JZ; Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan, USA., Emmer BT; Department of Internal Medicine, Division of Hospital Medicine, University of Michigan, Ann Arbor, Michigan, USA., Wobus CE; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, USA. |
| المصدر: | The Journal of general virology [J Gen Virol] 2023 Jun; Vol. 104 (6). |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: Microbiology Society Country of Publication: England NLM ID: 0077340 Publication Model: Print Cited Medium: Internet ISSN: 1465-2099 (Electronic) Linking ISSN: 00221317 NLM ISO Abbreviation: J Gen Virol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2015- : London : Microbiology Society Original Publication: London, Cambridge Univ. Press for the Society for General Microbiology. |
| مواضيع طبية MeSH: | COVID-19*, Humans ; ADP-Ribosylation Factor 6 ; Antiviral Agents/pharmacology ; SARS-CoV-2/metabolism ; Spike Glycoprotein, Coronavirus/metabolism ; Virus Internalization |
| مستخلص: | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly emerged beta-coronavirus that enter cells via two routes, direct fusion at the plasma membrane or endocytosis followed by fusion with the late endosome/lysosome. While the viral receptor, ACE2, multiple entry factors and the mechanism of fusion of the virus at the plasma membrane have been investigated extensively, viral entry via the endocytic pathway is less understood. By using a human hepatocarcinoma cell line, Huh-7, which is resistant to the antiviral action of the TMPRSS2 inhibitor camostat, we discovered that SARS-CoV-2 entry is not dependent on dynamin but on cholesterol. ADP-ribosylation factor 6 (ARF6) has been described as a host factor for SARS-CoV-2 replication and is involved in the entry and infection of several pathogenic viruses. Using CRISPR/Cas9 genetic deletion, a modest reduction in SARS-CoV-2 uptake and infection in Huh-7 was observed. In addition, pharmacological inhibition of ARF6 with the small molecule NAV-2729 showed a dose-dependent reduction of viral infection. Importantly, NAV-2729 also reduced SARS-CoV-2 viral loads in more physiological models of infection: Calu-3 cells and kidney organoids. This highlighted a role for ARF6 in multiple cell contexts. Together, these experiments point to ARF6 as a putative target to develop antiviral strategies against SARS-CoV-2. |
| التعليقات: | Update of: bioRxiv. 2022 Nov 07:2022.06.09.495482. doi: 10.1101/2022.06.09.495482. (PMID: 35702152) |
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| معلومات مُعتمدة: | UM1 TR004404 United States TR NCATS NIH HHS; T32 GM007767 United States GM NIGMS NIH HHS; K08 HL148552 United States HL NHLBI NIH HHS; R01 DK120623 United States DK NIDDK NIH HHS; UL1 TR002240 United States TR NCATS NIH HHS |
| فهرسة مساهمة: | Keywords: ARF6; SARS-CoV-2; endocytic pathway; entry; therapeutic targets |
| المشرفين على المادة: | 0 (ADP-Ribosylation Factor 6) 0 (Antiviral Agents) 0 (NAV-2729) 0 (Spike Glycoprotein, Coronavirus) 0 (spike protein, SARS-CoV-2) EC 3.6.5.2 (ARF6 protein, human) |
| تواريخ الأحداث: | Date Created: 20230621 Date Completed: 20230626 Latest Revision: 20240718 |
| رمز التحديث: | 20240718 |
| مُعرف محوري في PubMed: | PMC10397720 |
| DOI: | 10.1099/jgv.0.001868 |
| PMID: | 37342971 |
| قاعدة البيانات: | MEDLINE |
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