MicroRNA antagonism of the picornaviral life cycle: alternative mechanisms of interference.

dc.contributor.author

Kelly, Elizabeth J

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Hadac, Elizabeth M

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Cullen, Bryan R

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Russell, Stephen J

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United States

dc.date.accessioned

2011-06-21T17:32:22Z

dc.date.issued

2010-03-19

dc.description.abstract

In addition to modulating the function and stability of cellular mRNAs, microRNAs can profoundly affect the life cycles of viruses bearing sequence complementary targets, a finding recently exploited to ameliorate toxicities of vaccines and oncolytic viruses. To elucidate the mechanisms underlying microRNA-mediated antiviral activity, we modified the 3' untranslated region (3'UTR) of Coxsackievirus A21 to incorporate targets with varying degrees of homology to endogenous microRNAs. We show that microRNAs can interrupt the picornavirus life-cycle at multiple levels, including catalytic degradation of the viral RNA genome, suppression of cap-independent mRNA translation, and interference with genome encapsidation. In addition, we have examined the extent to which endogenous microRNAs can suppress viral replication in vivo and how viruses can overcome this inhibition by microRNA saturation in mouse cancer models.

dc.description.version

Version of Record

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http://www.ncbi.nlm.nih.gov/pubmed/20333250

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1553-7374

dc.identifier.uri

https://hdl.handle.net/10161/4597

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eng

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en_US

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Public Library of Science (PLoS)

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PLoS Pathog

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10.1371/journal.ppat.1000820

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Plos Pathogens

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3' Untranslated Regions

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Animals

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Base Sequence

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Cancer Vaccines

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Coxsackievirus Infections

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Disease Models, Animal

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Enterovirus

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HeLa Cells

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Humans

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Leukemia, Lymphocytic, Chronic, B-Cell

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Melanoma

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Mice

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Mice, SCID

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MicroRNAs

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Molecular Sequence Data

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Mutagenesis

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Neoplasm Transplantation

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Protein Biosynthesis

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RNA Interference

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RNA, Viral

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Transplantation, Heterologous

dc.title

MicroRNA antagonism of the picornaviral life cycle: alternative mechanisms of interference.

dc.title.alternative
dc.type

Journal article

duke.contributor.orcid

Cullen, Bryan R|0000-0002-8638-6850

duke.date.pubdate

2010-3-0

duke.description.issue

3

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6

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/20333250

pubs.begin-page

e1000820

pubs.issue

3

pubs.organisational-group

Basic Science Departments

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Clinical Science Departments

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Duke

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Duke Cancer Institute

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Institutes and Centers

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Medicine

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Medicine, Rheumatology and Immunology

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Molecular Genetics and Microbiology

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School of Medicine

pubs.publication-status

Published online

pubs.volume

6

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