دورية أكاديمية
أعرض في EDS

Cooperativity between the 3' untranslated region microRNA binding sites is critical for the virulence of eastern equine encephalitis virus.

التفاصيل البيبلوغرافية
العنوان: Cooperativity between the 3' untranslated region microRNA binding sites is critical for the virulence of eastern equine encephalitis virus.
المؤلفون: Trobaugh DW; Center for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America., Sun C; Center for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America., Bhalla N; Center for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America., Gardner CL; Center for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America., Dunn MD; Center for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America., Klimstra WB; Center for Vaccine Research, Department of Immunology and Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA United States of America.
المصدر: PLoS pathogens [PLoS Pathog] 2019 Oct 28; Vol. 15 (10), pp. e1007867. Date of Electronic Publication: 2019 Oct 28 (Print Publication: 2019).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, c2005-
مواضيع طبية MeSH: 3' Untranslated Regions/*genetics , Encephalitis Virus, Eastern Equine/*genetics , Encephalitis Virus, Western Equine/*genetics , MicroRNAs/*genetics , Virus Replication/*genetics, Aedes ; Animals ; Binding Sites/genetics ; Cell Line ; Cricetinae ; Encephalitis Virus, Eastern Equine/immunology ; Encephalitis Virus, Eastern Equine/pathogenicity ; Encephalitis Virus, Western Equine/immunology ; Encephalitis Virus, Western Equine/pathogenicity ; Encephalomyelitis, Equine/immunology ; Encephalomyelitis, Equine/virology ; Female ; Immunity, Innate/immunology ; L Cells ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; RAW 264.7 Cells ; Virulence/genetics
مستخلص: Eastern equine encephalitis virus (EEEV), a mosquito-borne RNA virus, is one of the most acutely virulent viruses endemic to the Americas, causing between 30% and 70% mortality in symptomatic human cases. A major factor in the virulence of EEEV is the presence of four binding sites for the hematopoietic cell-specific microRNA, miR-142-3p, in the 3' untranslated region (3' UTR) of the virus. Three of the sites are "canonical" with all 7 seed sequence residues complimentary to miR-142-3p while one is "non-canonical" and has a seed sequence mismatch. Interaction of the EEEV genome with miR-142-3p limits virus replication in myeloid cells and suppresses the systemic innate immune response, greatly exacerbating EEEV neurovirulence. The presence of the miRNA binding sequences is also required for efficient EEEV replication in mosquitoes and, therefore, essential for transmission of the virus. In the current studies, we have examined the role of each binding site by point mutagenesis of the seed sequences in all combinations of sites followed by infection of mammalian myeloid cells, mosquito cells and mice. The resulting data indicate that both canonical and non-canonical sites contribute to cell infection and animal virulence, however, surprisingly, all sites are rapidly deleted from EEEV genomes shortly after infection of myeloid cells or mice. Finally, we show that the virulence of a related encephalitis virus, western equine encephalitis virus, is also dependent upon miR-142-3p binding sites.
Competing Interests: The authors have declared that no competing interests exist
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معلومات مُعتمدة: R01 AI095436 United States AI NIAID NIH HHS; R21 AI111115 United States AI NIAID NIH HHS; R21 AI132909 United States AI NIAID NIH HHS
المشرفين على المادة: 0 (3' Untranslated Regions)
0 (MicroRNAs)
0 (Mirn142 microRNA, mouse)
تواريخ الأحداث: Date Created: 20191029 Date Completed: 20200203 Latest Revision: 20201213
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6936876
DOI: 10.1371/journal.ppat.1007867
PMID: 31658290
قاعدة البيانات: MEDLINE
الوصف
تدمد:1553-7374
DOI:10.1371/journal.ppat.1007867