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Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity
Analysis of the incorporation of cellular microRNAs (miRNAs) into highly purified HIV-1 virions revealed that this largely, but not entirely, mirrored the level of miRNA expression in the producer CD4(+) T cells. Specifically, of the 58 cellular miRNAs detected at significant levels in the producer...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Microbiology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241401/ https://www.ncbi.nlm.nih.gov/pubmed/28096489 http://dx.doi.org/10.1128/mBio.02125-16 |
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author | Bogerd, Hal P. Kennedy, Edward M. Whisnant, Adam W. Cullen, Bryan R. |
author_facet | Bogerd, Hal P. Kennedy, Edward M. Whisnant, Adam W. Cullen, Bryan R. |
author_sort | Bogerd, Hal P. |
collection | PubMed |
description | Analysis of the incorporation of cellular microRNAs (miRNAs) into highly purified HIV-1 virions revealed that this largely, but not entirely, mirrored the level of miRNA expression in the producer CD4(+) T cells. Specifically, of the 58 cellular miRNAs detected at significant levels in the producer cells, only 5 were found in virions at a level 2- to 4-fold higher than that predicted on the basis of random cytoplasmic sampling. Of note, these included two miRNAs, miR-155 and miR-92a, that were reported previously to at least weakly bind HIV-1 transcripts. To test whether miRNA binding to the HIV-1 genome can induce virion incorporation, artificial miRNA target sites were introduced into the viral genome and a 10- to 40-fold increase in the packaging of the cognate miRNAs into virions was then observed, leading to the recruitment of up to 1.6 miRNA copies per virion. Importantly, this high level of incorporation significantly inhibited HIV-1 virion infectivity. These results suggest that target sites for cellular miRNAs can inhibit RNA virus replication at two distinct steps, i.e., during infection and during viral gene expression, thus explaining why a range of different RNA viruses appear to have evolved to avoid cellular miRNA binding to their genome. |
format | Online Article Text |
id | pubmed-5241401 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | American Society for Microbiology |
record_format | MEDLINE/PubMed |
spelling | pubmed-52414012017-01-18 Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity Bogerd, Hal P. Kennedy, Edward M. Whisnant, Adam W. Cullen, Bryan R. mBio Research Article Analysis of the incorporation of cellular microRNAs (miRNAs) into highly purified HIV-1 virions revealed that this largely, but not entirely, mirrored the level of miRNA expression in the producer CD4(+) T cells. Specifically, of the 58 cellular miRNAs detected at significant levels in the producer cells, only 5 were found in virions at a level 2- to 4-fold higher than that predicted on the basis of random cytoplasmic sampling. Of note, these included two miRNAs, miR-155 and miR-92a, that were reported previously to at least weakly bind HIV-1 transcripts. To test whether miRNA binding to the HIV-1 genome can induce virion incorporation, artificial miRNA target sites were introduced into the viral genome and a 10- to 40-fold increase in the packaging of the cognate miRNAs into virions was then observed, leading to the recruitment of up to 1.6 miRNA copies per virion. Importantly, this high level of incorporation significantly inhibited HIV-1 virion infectivity. These results suggest that target sites for cellular miRNAs can inhibit RNA virus replication at two distinct steps, i.e., during infection and during viral gene expression, thus explaining why a range of different RNA viruses appear to have evolved to avoid cellular miRNA binding to their genome. American Society for Microbiology 2017-01-17 /pmc/articles/PMC5241401/ /pubmed/28096489 http://dx.doi.org/10.1128/mBio.02125-16 Text en Copyright © 2017 Bogerd et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Bogerd, Hal P. Kennedy, Edward M. Whisnant, Adam W. Cullen, Bryan R. Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity |
title | Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity |
title_full | Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity |
title_fullStr | Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity |
title_full_unstemmed | Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity |
title_short | Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity |
title_sort | induced packaging of cellular micrornas into hiv-1 virions can inhibit infectivity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5241401/ https://www.ncbi.nlm.nih.gov/pubmed/28096489 http://dx.doi.org/10.1128/mBio.02125-16 |
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