دورية أكاديمية
أعرض في EDS

Determination of system level alterations in host transcriptome due to Zika virus (ZIKV) Infection in retinal pigment epithelium.

التفاصيل البيبلوغرافية
العنوان: Determination of system level alterations in host transcriptome due to Zika virus (ZIKV) Infection in retinal pigment epithelium.
المؤلفون: Singh PK; Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, MI, USA., Khatri I; BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Centre, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Jha A; BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Centre, Beth Israel Deaconess Medical Center, Boston, MA, USA.; Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Pretto CD; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA., Spindler KR; Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, USA., Arumugaswami V; Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA, USA., Giri S; Department of Neurology, Henry Ford Health System, Detroit, MI, USA., Kumar A; Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, Detroit, MI, USA. akuma@med.wayne.edu.; Department of Biochemistry, Microbiology, and Immunology, Wayne State University, Detroit, MI, USA. akuma@med.wayne.edu., Bhasin MK; BIDMC Genomics, Proteomics, Bioinformatics and Systems Biology Centre, Beth Israel Deaconess Medical Center, Boston, MA, USA. mbhasin@bidmc.harvard.edu.; Division of Interdisciplinary Medicine and Biotechnology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. mbhasin@bidmc.harvard.edu.
المصدر: Scientific reports [Sci Rep] 2018 Jul 25; Vol. 8 (1), pp. 11209. Date of Electronic Publication: 2018 Jul 25.
نوع المنشور: Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Retinal Pigment Epithelium/*metabolism , Transcriptome/*genetics , Zika Virus/*genetics , Zika Virus Infection/*genetics, ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics ; Adaptor Proteins, Signal Transducing ; B-Cell Activating Factor/genetics ; Dengue/genetics ; Dengue/pathology ; Dengue/virology ; Dengue Virus/pathogenicity ; Encephalitis Viruses, Japanese/pathogenicity ; Flavivirus Infections/genetics ; Flavivirus Infections/pathology ; Flavivirus Infections/virology ; Gene Expression Regulation/genetics ; Homeodomain Proteins/genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; Primary Cell Culture ; Proteins/genetics ; Retinal Pigment Epithelium/pathology ; Retinal Pigment Epithelium/virology ; Trans-Activators/genetics ; Virus Replication/genetics ; West Nile Fever/genetics ; West Nile Fever/pathology ; West Nile Fever/virology ; West Nile virus/pathogenicity ; Zika Virus/pathogenicity ; Zika Virus Infection/pathology ; Zika Virus Infection/virology
مستخلص: Previously, we reported that Zika virus (ZIKV) causes ocular complications such as chorioretinal atrophy, by infecting cells lining the blood-retinal barrier, including the retinal pigment epithelium (RPE). To understand the molecular basis of ZIKV-induced retinal pathology, we performed a meta-analysis of transcriptome profiles of ZIKV-infected human primary RPE and other cell types infected with either ZIKV or other related flaviviruses (Japanese encephalitis, West Nile, and Dengue). This led to identification of a unique ZIKV infection signature comprising 43 genes (35 upregulated and 8 downregulated). The major biological processes perturbed include SH3/SH2 adaptor activity, lipid and ceramide metabolism, and embryonic organ development. Further, a comparative analysis of some differentially regulated genes (ABCG1, SH2B3, SIX4, and TNFSF13B) revealed that ZIKV induced their expression relatively more than dengue virus did in RPE. Importantly, the pharmacological inhibition of ABCG1, a membrane transporter of cholesterol, resulted in reduced ZIKV infectivity. Interestingly, the ZIKV infection signature revealed the downregulation of ALDH5A1 and CHML, genes implicated in neurological (cognitive impairment, expressive language deficit, and mild ataxia) and ophthalmic (choroideremia) disorders, respectively. Collectively, our study revealed that ZIKV induces differential gene expression in RPE cells, and the identified genes/pathways (e.g., ABCG1) could potentially contribute to ZIKV-associated ocular pathologies.
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معلومات مُعتمدة: R01 EY026964 United States EY NEI NIH HHS; R21 AI135583 United States AI NIAID NIH HHS; R01 EY027381 United States EY NEI NIH HHS; R01 AI091721 United States AI NIAID NIH HHS; P30 EY004068 United States EY NEI NIH HHS
المشرفين على المادة: 0 (ABCG1 protein, human)
0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
0 (Adaptor Proteins, Signal Transducing)
0 (B-Cell Activating Factor)
0 (Homeodomain Proteins)
0 (Intracellular Signaling Peptides and Proteins)
0 (Proteins)
0 (SH2B3 protein, human)
0 (SIX4 protein, human)
0 (Trans-Activators)
تواريخ الأحداث: Date Created: 20180727 Date Completed: 20191014 Latest Revision: 20240329
رمز التحديث: 20240329
مُعرف محوري في PubMed: PMC6060127
DOI: 10.1038/s41598-018-29329-2
PMID: 30046058
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-018-29329-2