Respiratory Syncytial Virus Regulates Human MicroRNAs by Using Mechanisms Involving Beta Interferon and NF-κB

ABSTRACT Respiratory syncytial virus (RSV) is the most common viral cause of severe lower respiratory tract illness in infants and children. The virus replicates in polarized epithelial cells in the airway and, to a lesser extent, infects airway antigen-presenting cells, such as dendritic cells (DCs...

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Autores principales:	Natalie J. Thornburg, Sarah L. Hayward, James E. Crowe
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2012
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/81d852e0441447de97bf1bb118ca5bfc
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spelling	oai:doaj.org-article:81d852e0441447de97bf1bb118ca5bfc2021-11-15T15:39:11ZRespiratory Syncytial Virus Regulates Human MicroRNAs by Using Mechanisms Involving Beta Interferon and NF-κB10.1128/mBio.00220-122150-7511https://doaj.org/article/81d852e0441447de97bf1bb118ca5bfc2012-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00220-12https://doaj.org/toc/2150-7511ABSTRACT Respiratory syncytial virus (RSV) is the most common viral cause of severe lower respiratory tract illness in infants and children. The virus replicates in polarized epithelial cells in the airway and, to a lesser extent, infects airway antigen-presenting cells, such as dendritic cells (DCs). RSV possesses a number of expressed genes that antagonize the effect of type I interferons and other related host factor pathways that inhibit replication efficiency. Virus infection alters host gene transcription and the translation of host transcripts through specific antagonism of the function of host proteins, through induction of RNA stress granules, and through induction of altered patterns of host gene expression. In healthy cells, microRNAs (miRNAs) regulate gene expression by targeting the noncoding region of mRNA molecules to cause silencing or degradation of transcripts. It is not known whether or not RSV infection alters the level of microRNAs in cells. We profiled the pattern of expression of host cell microRNAs in RSV-infected epithelial cells or DCs and found that RSV did alter microRNA expression but in a cell-type-specific manner. The studies showed that let-7b was upregulated in DCs, while let-7i and miR-30b were upregulated in epithelial cells in a process that required viral replication. Interestingly, we found that the RSV nonstructural genes NS1 and NS2 antagonized the upregulation of let-7i and miR-30b. RSV appears to manipulate host cell gene expression through regulation of expression of miRNAs related to the interferon response. The data suggest a new mechanism of virus-host cell interactions for paramyxoviruses. IMPORTANCE Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory tract illness in infants and children. The human innate immune response inhibits RSV replication early after inoculation, principally through the effect of substances called interferons. The virus, however, has developed several mechanisms for counteracting the host innate immune response. It is not known whether or not RSV infection alters the expression of host microRNAs, which are short RNA sequences that are posttranscriptional regulators. This paper shows that RSV does induce unique patterns of microRNA expression related to the NF-κB pathway or interferon pathways. The microRNA profiles differed depending on the cell type that was infected, airway cell or antigen-presenting cell. Interestingly, the virus appears to counteract the microRNA response by expressing nonstructural viral genes in the cell that reduce microRNA induction. The data suggest a new way in which paramyxoviruses regulate the host cell response to infection.Natalie J. ThornburgSarah L. HaywardJames E. CroweAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 3, Iss 6 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Natalie J. Thornburg Sarah L. Hayward James E. Crowe Respiratory Syncytial Virus Regulates Human MicroRNAs by Using Mechanisms Involving Beta Interferon and NF-κB
description	ABSTRACT Respiratory syncytial virus (RSV) is the most common viral cause of severe lower respiratory tract illness in infants and children. The virus replicates in polarized epithelial cells in the airway and, to a lesser extent, infects airway antigen-presenting cells, such as dendritic cells (DCs). RSV possesses a number of expressed genes that antagonize the effect of type I interferons and other related host factor pathways that inhibit replication efficiency. Virus infection alters host gene transcription and the translation of host transcripts through specific antagonism of the function of host proteins, through induction of RNA stress granules, and through induction of altered patterns of host gene expression. In healthy cells, microRNAs (miRNAs) regulate gene expression by targeting the noncoding region of mRNA molecules to cause silencing or degradation of transcripts. It is not known whether or not RSV infection alters the level of microRNAs in cells. We profiled the pattern of expression of host cell microRNAs in RSV-infected epithelial cells or DCs and found that RSV did alter microRNA expression but in a cell-type-specific manner. The studies showed that let-7b was upregulated in DCs, while let-7i and miR-30b were upregulated in epithelial cells in a process that required viral replication. Interestingly, we found that the RSV nonstructural genes NS1 and NS2 antagonized the upregulation of let-7i and miR-30b. RSV appears to manipulate host cell gene expression through regulation of expression of miRNAs related to the interferon response. The data suggest a new mechanism of virus-host cell interactions for paramyxoviruses. IMPORTANCE Respiratory syncytial virus (RSV) is the most common cause of serious lower respiratory tract illness in infants and children. The human innate immune response inhibits RSV replication early after inoculation, principally through the effect of substances called interferons. The virus, however, has developed several mechanisms for counteracting the host innate immune response. It is not known whether or not RSV infection alters the expression of host microRNAs, which are short RNA sequences that are posttranscriptional regulators. This paper shows that RSV does induce unique patterns of microRNA expression related to the NF-κB pathway or interferon pathways. The microRNA profiles differed depending on the cell type that was infected, airway cell or antigen-presenting cell. Interestingly, the virus appears to counteract the microRNA response by expressing nonstructural viral genes in the cell that reduce microRNA induction. The data suggest a new way in which paramyxoviruses regulate the host cell response to infection.
format	article
author	Natalie J. Thornburg Sarah L. Hayward James E. Crowe
author_facet	Natalie J. Thornburg Sarah L. Hayward James E. Crowe
author_sort	Natalie J. Thornburg
title	Respiratory Syncytial Virus Regulates Human MicroRNAs by Using Mechanisms Involving Beta Interferon and NF-κB
title_short	Respiratory Syncytial Virus Regulates Human MicroRNAs by Using Mechanisms Involving Beta Interferon and NF-κB
title_full	Respiratory Syncytial Virus Regulates Human MicroRNAs by Using Mechanisms Involving Beta Interferon and NF-κB
title_fullStr	Respiratory Syncytial Virus Regulates Human MicroRNAs by Using Mechanisms Involving Beta Interferon and NF-κB
title_full_unstemmed	Respiratory Syncytial Virus Regulates Human MicroRNAs by Using Mechanisms Involving Beta Interferon and NF-κB
title_sort	respiratory syncytial virus regulates human micrornas by using mechanisms involving beta interferon and nf-κb
publisher	American Society for Microbiology
publishDate	2012
url	https://doaj.org/article/81d852e0441447de97bf1bb118ca5bfc
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Respiratory Syncytial Virus Regulates Human MicroRNAs by Using Mechanisms Involving Beta Interferon and NF-κB

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