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Adenovirus-Encoding Virus-Associated RNAs Suppress HDGF Gene Expression to Support Efficient Viral Replication

Non-coding small RNAs are involved in many physiological responses including viral life cycles. Adenovirus-encoding small RNAs, known as virus-associated RNAs (VA RNAs), are transcribed throughout the replication process in the host cells, and their transcript levels depend on the copy numbers of th...

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Autores principales: Kondo, Saki, Yoshida, Kenji, Suzuki, Mariko, Saito, Izumu, Kanegae, Yumi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183520/
https://www.ncbi.nlm.nih.gov/pubmed/25275311
http://dx.doi.org/10.1371/journal.pone.0108627
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author Kondo, Saki
Yoshida, Kenji
Suzuki, Mariko
Saito, Izumu
Kanegae, Yumi
author_facet Kondo, Saki
Yoshida, Kenji
Suzuki, Mariko
Saito, Izumu
Kanegae, Yumi
author_sort Kondo, Saki
collection PubMed
description Non-coding small RNAs are involved in many physiological responses including viral life cycles. Adenovirus-encoding small RNAs, known as virus-associated RNAs (VA RNAs), are transcribed throughout the replication process in the host cells, and their transcript levels depend on the copy numbers of the viral genome. Therefore, VA RNAs are abundant in infected cells after genome replication, i.e. during the late phase of viral infection. Their function during the late phase is the inhibition of interferon-inducible protein kinase R (PKR) activity to prevent antiviral responses; recently, mivaRNAs, the microRNAs processed from VA RNAs, have been reported to inhibit cellular gene expression. Although VA RNA transcription starts during the early phase, little is known about its function. The reason may be because much smaller amount of VA RNAs are transcribed during the early phase than the late phase. In this study, we applied replication-deficient adenovirus vectors (AdVs) and novel AdVs lacking VA RNA genes to analyze the expression changes in cellular genes mediated by VA RNAs using microarray analysis. AdVs are suitable to examine the function of VA RNAs during the early phase, since they constitutively express VA RNAs but do not replicate except in 293 cells. We found that the expression level of hepatoma-derived growth factor (HDGF) significantly decreased in response to the VA RNAs under replication-deficient condition, and this suppression was also observed during the early phase under replication-competent conditions. The suppression was independent of mivaRNA-induced downregulation, suggesting that the function of VA RNAs during the early phase differs from that during the late phase. Notably, overexpression of HDGF inhibited AdV growth. This is the first report to show the function, in part, of VA RNAs during the early phase that may be contribute to efficient viral growth.
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spelling pubmed-41835202014-10-07 Adenovirus-Encoding Virus-Associated RNAs Suppress HDGF Gene Expression to Support Efficient Viral Replication Kondo, Saki Yoshida, Kenji Suzuki, Mariko Saito, Izumu Kanegae, Yumi PLoS One Research Article Non-coding small RNAs are involved in many physiological responses including viral life cycles. Adenovirus-encoding small RNAs, known as virus-associated RNAs (VA RNAs), are transcribed throughout the replication process in the host cells, and their transcript levels depend on the copy numbers of the viral genome. Therefore, VA RNAs are abundant in infected cells after genome replication, i.e. during the late phase of viral infection. Their function during the late phase is the inhibition of interferon-inducible protein kinase R (PKR) activity to prevent antiviral responses; recently, mivaRNAs, the microRNAs processed from VA RNAs, have been reported to inhibit cellular gene expression. Although VA RNA transcription starts during the early phase, little is known about its function. The reason may be because much smaller amount of VA RNAs are transcribed during the early phase than the late phase. In this study, we applied replication-deficient adenovirus vectors (AdVs) and novel AdVs lacking VA RNA genes to analyze the expression changes in cellular genes mediated by VA RNAs using microarray analysis. AdVs are suitable to examine the function of VA RNAs during the early phase, since they constitutively express VA RNAs but do not replicate except in 293 cells. We found that the expression level of hepatoma-derived growth factor (HDGF) significantly decreased in response to the VA RNAs under replication-deficient condition, and this suppression was also observed during the early phase under replication-competent conditions. The suppression was independent of mivaRNA-induced downregulation, suggesting that the function of VA RNAs during the early phase differs from that during the late phase. Notably, overexpression of HDGF inhibited AdV growth. This is the first report to show the function, in part, of VA RNAs during the early phase that may be contribute to efficient viral growth. Public Library of Science 2014-10-02 /pmc/articles/PMC4183520/ /pubmed/25275311 http://dx.doi.org/10.1371/journal.pone.0108627 Text en © 2014 Kondo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kondo, Saki
Yoshida, Kenji
Suzuki, Mariko
Saito, Izumu
Kanegae, Yumi
Adenovirus-Encoding Virus-Associated RNAs Suppress HDGF Gene Expression to Support Efficient Viral Replication
title Adenovirus-Encoding Virus-Associated RNAs Suppress HDGF Gene Expression to Support Efficient Viral Replication
title_full Adenovirus-Encoding Virus-Associated RNAs Suppress HDGF Gene Expression to Support Efficient Viral Replication
title_fullStr Adenovirus-Encoding Virus-Associated RNAs Suppress HDGF Gene Expression to Support Efficient Viral Replication
title_full_unstemmed Adenovirus-Encoding Virus-Associated RNAs Suppress HDGF Gene Expression to Support Efficient Viral Replication
title_short Adenovirus-Encoding Virus-Associated RNAs Suppress HDGF Gene Expression to Support Efficient Viral Replication
title_sort adenovirus-encoding virus-associated rnas suppress hdgf gene expression to support efficient viral replication
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4183520/
https://www.ncbi.nlm.nih.gov/pubmed/25275311
http://dx.doi.org/10.1371/journal.pone.0108627
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