دورية أكاديمية
أعرض في EDS

BIKE regulates dengue virus infection and is a cellular target for broad-spectrum antivirals.

التفاصيل البيبلوغرافية
العنوان: BIKE regulates dengue virus infection and is a cellular target for broad-spectrum antivirals.
المؤلفون: Pu S; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Department of Microbiology and Immunology, Stanford University, CA, USA., Schor S; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Department of Microbiology and Immunology, Stanford University, CA, USA., Karim M; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Department of Microbiology and Immunology, Stanford University, CA, USA., Saul S; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Department of Microbiology and Immunology, Stanford University, CA, USA., Robinson M; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Department of Microbiology and Immunology, Stanford University, CA, USA., Kumar S; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Department of Microbiology and Immunology, Stanford University, CA, USA., Prugar LI; US Army Medical Research Institute of Infectious Diseases, Viral Immunology Branch, Fort Detrick, Maryland, USA., Dorosky DE; US Army Medical Research Institute of Infectious Diseases, Viral Immunology Branch, Fort Detrick, Maryland, USA., Brannan J; US Army Medical Research Institute of Infectious Diseases, Viral Immunology Branch, Fort Detrick, Maryland, USA., Dye JM; US Army Medical Research Institute of Infectious Diseases, Viral Immunology Branch, Fort Detrick, Maryland, USA., Einav S; Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Department of Microbiology and Immunology, Stanford University, CA, USA. Electronic address: seinav@stanford.edu.
المصدر: Antiviral research [Antiviral Res] 2020 Dec; Vol. 184, pp. 104966. Date of Electronic Publication: 2020 Nov 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8109699 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-9096 (Electronic) Linking ISSN: 01663542 NLM ISO Abbreviation: Antiviral Res Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: [Amsterdam ; New York : Elsevier/North-Holland Biomedical Press, c1981-
مواضيع طبية MeSH: Dengue/*virology , Dengue Virus/*physiology , Lactones/*pharmacology , Protein Serine-Threonine Kinases/*physiology , Resorcinols/*pharmacology , Transcription Factors/*physiology, Adaptor Proteins, Vesicular Transport/antagonists & inhibitors ; Animals ; Antiviral Agents/pharmacology ; Cell Line ; Chlorocebus aethiops ; Dengue/drug therapy ; Dengue Virus/drug effects ; Drug Repositioning ; Host Microbial Interactions ; Humans ; Intracellular Signaling Peptides and Proteins/physiology ; Phosphorylation ; Protein Kinase Inhibitors/pharmacology ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; RNA, Viral ; Recombinant Proteins ; Signal Transduction ; Vero Cells ; Virus Internalization ; Virus Replication
مستخلص: Global health is threatened by emerging viruses, many of which lack approved therapies and effective vaccines, including dengue, Ebola, and Venezuelan equine encephalitis. We previously reported that AAK1 and GAK, two of the four members of the understudied Numb-associated kinases (NAK) family, control intracellular trafficking of RNA viruses. Nevertheless, the role of BIKE and STK16 in viral infection remained unknown. Here, we reveal a requirement for BIKE, but not STK-16, in dengue virus (DENV) infection. BIKE mediates both early (postinternalization) and late (assembly/egress) stages in the DENV life cycle, and this effect is mediated in part by phosphorylation of a threonine 156 (T156) residue in the μ subunit of the adaptor protein (AP) 2 complex. Pharmacological compounds with potent anti-BIKE activity, including the investigational anticancer drug 5Z-7-oxozeaenol and more selective inhibitors, suppress DENV infection both in vitro and ex vivo. BIKE overexpression reverses the antiviral activity, validating that the mechanism of antiviral action is, at least in part, mediated by BIKE. Lastly, 5Z-7-oxozeaenol exhibits antiviral activity against viruses from three unrelated RNA viral families with a high genetic barrier to resistance. These findings reveal regulation of poorly understood stages of the DENV life cycle via BIKE signaling and establish a proof-of-principle that pharmacological inhibition of BIKE can be potentially used as a broad-spectrum strategy against acute emerging viral infections.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
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معلومات مُعتمدة: U19 AI109662 United States AI NIAID NIH HHS; UL1 TR000093 United States TR NCATS NIH HHS; UL1 TR003142 United States TR NCATS NIH HHS; UL1 TR000090 United States TR NCATS NIH HHS
فهرسة مساهمة: Keywords: Antivirals; Dengue virus; Drug repurposing; Kinase inhibitors; Virus-host interactions
المشرفين على المادة: 0 (7-oxozeanol)
0 (AP2M1 protein, human)
0 (Adaptor Proteins, Vesicular Transport)
0 (Antiviral Agents)
0 (Intracellular Signaling Peptides and Proteins)
0 (Lactones)
0 (Protein Kinase Inhibitors)
0 (RNA, Viral)
0 (Recombinant Proteins)
0 (Resorcinols)
0 (Transcription Factors)
EC 2.7.11.1 (AAK1 protein, human)
EC 2.7.11.1 (Protein Serine-Threonine Kinases)
EC 2.7.11.1 (STK16 protein, human)
تواريخ الأحداث: Date Created: 20201102 Date Completed: 20210726 Latest Revision: 20220304
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7879702
DOI: 10.1016/j.antiviral.2020.104966
PMID: 33137362
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-9096
DOI:10.1016/j.antiviral.2020.104966