Publication Date:
2013-12-20
Description:
Currently, there is little evidence for a notable role of the vertebrate microRNA (miRNA) system in the pathogenesis of RNA viruses. This is primarily attributed to the ease with which these viruses mutate to disrupt recognition and growth suppression by host miRNAs. Here we report that the haematopoietic-cell-specific miRNA miR-142-3p potently restricts the replication of the mosquito-borne North American eastern equine encephalitis virus in myeloid-lineage cells by binding to sites in the 3' non-translated region of its RNA genome. However, by limiting myeloid cell tropism and consequent innate immunity induction, this restriction directly promotes neurologic disease manifestations characteristic of eastern equine encephalitis virus infection in humans. Furthermore, the region containing the miR-142-3p binding sites is essential for efficient virus infection of mosquito vectors. We propose that RNA viruses can adapt to use antiviral properties of vertebrate miRNAs to limit replication in particular cell types and that this restriction can lead to exacerbation of disease severity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349380/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349380/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Trobaugh, Derek W -- Gardner, Christina L -- Sun, Chengqun -- Haddow, Andrew D -- Wang, Eryu -- Chapnik, Elik -- Mildner, Alexander -- Weaver, Scott C -- Ryman, Kate D -- Klimstra, William B -- AI049820-10/AI/NIAID NIH HHS/ -- AI060525-08/AI/NIAID NIH HHS/ -- AI083383/AI/NIAID NIH HHS/ -- AI095436/AI/NIAID NIH HHS/ -- R01 AI083383/AI/NIAID NIH HHS/ -- R01 AI095436/AI/NIAID NIH HHS/ -- T32 AI060525/AI/NIAID NIH HHS/ -- U54 AI081680/AI/NIAID NIH HHS/ -- England -- Nature. 2014 Feb 13;506(7487):245-8. doi: 10.1038/nature12869. Epub 2013 Dec 18.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Center for Vaccine Research and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. ; Institute for Human Infections and Immunity, Center for Biodefense and Emerging Infectious Diseases, and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555, USA. ; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 7610001, Israel. ; Department of Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24352241" target="_blank"〉PubMed〈/a〉
Keywords:
3' Untranslated Regions/genetics
;
Alphavirus Infections/immunology/pathology/virology
;
Animals
;
Binding Sites/genetics
;
Cell Line
;
Cricetinae
;
Culicidae/virology
;
Disease Models, Animal
;
Encephalitis Virus, Eastern Equine/genetics/growth &
;
development/*immunology/*pathogenicity
;
Female
;
*Host-Pathogen Interactions/immunology
;
*Immune Evasion/genetics
;
Immunity, Innate/genetics/*immunology
;
Insect Vectors/virology
;
Male
;
Mice
;
MicroRNAs/*genetics/metabolism
;
Myeloid Cells/immunology/virology
;
Organ Specificity
;
Virus Replication/genetics/immunology
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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