Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity

ABSTRACT 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 pr...

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Autores principales:	Hal P. Bogerd, Edward M. Kennedy, Adam W. Whisnant, Bryan R. Cullen
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fa069fe78e4a48ef9bd34dcaee41438c
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spelling	oai:doaj.org-article:fa069fe78e4a48ef9bd34dcaee41438c2021-11-15T15:51:07ZInduced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity10.1128/mBio.02125-162150-7511https://doaj.org/article/fa069fe78e4a48ef9bd34dcaee41438c2017-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02125-16https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE The genomes of RNA viruses have the potential to interact with cellular miRNAs, which could lead to their incorporation into virions, with unknown effects on virion function. Here, it is demonstrated that wild-type HIV-1 virions essentially randomly incorporate low levels of the miRNAs expressed by infected cells. However, the specific incorporation of high levels of individual cellular miRNAs can be induced by insertion of cognate target sites into the viral genome. Of note, this results in a modest but significant inhibition of virion infectivity. These data imply that cellular miRNAs have the potential to inhibit viral replication by interfering with not only viral mRNA function but also virion infectivity.Hal P. BogerdEdward M. KennedyAdam W. WhisnantBryan R. CullenAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 1 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Hal P. Bogerd Edward M. Kennedy Adam W. Whisnant Bryan R. Cullen Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity
description	ABSTRACT 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. IMPORTANCE The genomes of RNA viruses have the potential to interact with cellular miRNAs, which could lead to their incorporation into virions, with unknown effects on virion function. Here, it is demonstrated that wild-type HIV-1 virions essentially randomly incorporate low levels of the miRNAs expressed by infected cells. However, the specific incorporation of high levels of individual cellular miRNAs can be induced by insertion of cognate target sites into the viral genome. Of note, this results in a modest but significant inhibition of virion infectivity. These data imply that cellular miRNAs have the potential to inhibit viral replication by interfering with not only viral mRNA function but also virion infectivity.
format	article
author	Hal P. Bogerd Edward M. Kennedy Adam W. Whisnant Bryan R. Cullen
author_facet	Hal P. Bogerd Edward M. Kennedy Adam W. Whisnant Bryan R. Cullen
author_sort	Hal P. Bogerd
title	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_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_sort	induced packaging of cellular micrornas into hiv-1 virions can inhibit infectivity
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/fa069fe78e4a48ef9bd34dcaee41438c
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Induced Packaging of Cellular MicroRNAs into HIV-1 Virions Can Inhibit Infectivity

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