Nucleolar Relocalization of RBM14 by Influenza A Virus NS1 Protein

ABSTRACT Viruses utilize a number of host factors in order to carry out their replication cycles. Influenza A virus (IAV) and human respiratory syncytial virus (RSV) both infect the tissues of the respiratory tract, and as such we hypothesize that they might require similar host factors. Several pub...

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Autores principales:	Grant Beyleveld, Daniel J. Chin, Elena Moreno Del Olmo, Jade Carter, Isabel Najera, Cristian Cillóniz, Megan L. Shaw
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	NS1 protein RNA interference influenza virus systems biology virus-host interactions Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/aef6b66200154570aa11ec6e8e032464
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spelling	oai:doaj.org-article:aef6b66200154570aa11ec6e8e0324642021-11-15T15:22:21ZNucleolar Relocalization of RBM14 by Influenza A Virus NS1 Protein10.1128/mSphereDirect.00549-182379-5042https://doaj.org/article/aef6b66200154570aa11ec6e8e0324642018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphereDirect.00549-18https://doaj.org/toc/2379-5042ABSTRACT Viruses utilize a number of host factors in order to carry out their replication cycles. Influenza A virus (IAV) and human respiratory syncytial virus (RSV) both infect the tissues of the respiratory tract, and as such we hypothesize that they might require similar host factors. Several published genome-wide screens have identified putative IAV host factors; however, there is significant discordance between their hits. In order to build on this work, we integrated a variety of “OMICS” data sources using two complementary network analyses, yielding 51 genes enriched for both IAV and RSV replication. We designed a targeted small interfering RNA (siRNA)-based assay to screen these genes against IAV under robust conditions and identified 13 genes supported by two IAV subtypes in both primary and transformed human lung cells. One of these hits, RNA binding motif 14 (RBM14), was validated as a required host factor and furthermore was shown to relocalize to the nucleolus upon IAV infection but not with other viruses. Additionally, the IAV NS1 protein is both necessary and sufficient for RBM14 relocalization, and relocalization also requires the double-stranded RNA (dsRNA) binding capacity of NS1. This work reports the discovery of a new host requirement for IAV replication and exposes a novel example of interplay between IAV NS1 and the host protein, RBM14. IMPORTANCE Influenza A virus (IAV) and respiratory syncytial virus (RSV) present major global disease burdens. There are high economic costs associated with morbidity as well as significant mortality rates, especially in developing countries, in children, and in the elderly. There are currently limited therapeutic options for these viruses, which underscores the need for novel research into virus biology that may lead to the discovery of new therapeutic approaches. This work extends existing research into host factors involved in virus replication and explores the interaction between IAV and one such host factor, RBM14. Further study to fully characterize this interaction may elucidate novel mechanisms used by the virus during its replication cycle and open new avenues for understanding virus biology.Grant BeyleveldDaniel J. ChinElena Moreno Del OlmoJade CarterIsabel NajeraCristian CillónizMegan L. ShawAmerican Society for MicrobiologyarticleNS1 proteinRNA interferenceinfluenza virussystems biologyvirus-host interactionsMicrobiologyQR1-502ENmSphere, Vol 3, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	NS1 protein RNA interference influenza virus systems biology virus-host interactions Microbiology QR1-502
spellingShingle	NS1 protein RNA interference influenza virus systems biology virus-host interactions Microbiology QR1-502 Grant Beyleveld Daniel J. Chin Elena Moreno Del Olmo Jade Carter Isabel Najera Cristian Cillóniz Megan L. Shaw Nucleolar Relocalization of RBM14 by Influenza A Virus NS1 Protein
description	ABSTRACT Viruses utilize a number of host factors in order to carry out their replication cycles. Influenza A virus (IAV) and human respiratory syncytial virus (RSV) both infect the tissues of the respiratory tract, and as such we hypothesize that they might require similar host factors. Several published genome-wide screens have identified putative IAV host factors; however, there is significant discordance between their hits. In order to build on this work, we integrated a variety of “OMICS” data sources using two complementary network analyses, yielding 51 genes enriched for both IAV and RSV replication. We designed a targeted small interfering RNA (siRNA)-based assay to screen these genes against IAV under robust conditions and identified 13 genes supported by two IAV subtypes in both primary and transformed human lung cells. One of these hits, RNA binding motif 14 (RBM14), was validated as a required host factor and furthermore was shown to relocalize to the nucleolus upon IAV infection but not with other viruses. Additionally, the IAV NS1 protein is both necessary and sufficient for RBM14 relocalization, and relocalization also requires the double-stranded RNA (dsRNA) binding capacity of NS1. This work reports the discovery of a new host requirement for IAV replication and exposes a novel example of interplay between IAV NS1 and the host protein, RBM14. IMPORTANCE Influenza A virus (IAV) and respiratory syncytial virus (RSV) present major global disease burdens. There are high economic costs associated with morbidity as well as significant mortality rates, especially in developing countries, in children, and in the elderly. There are currently limited therapeutic options for these viruses, which underscores the need for novel research into virus biology that may lead to the discovery of new therapeutic approaches. This work extends existing research into host factors involved in virus replication and explores the interaction between IAV and one such host factor, RBM14. Further study to fully characterize this interaction may elucidate novel mechanisms used by the virus during its replication cycle and open new avenues for understanding virus biology.
format	article
author	Grant Beyleveld Daniel J. Chin Elena Moreno Del Olmo Jade Carter Isabel Najera Cristian Cillóniz Megan L. Shaw
author_facet	Grant Beyleveld Daniel J. Chin Elena Moreno Del Olmo Jade Carter Isabel Najera Cristian Cillóniz Megan L. Shaw
author_sort	Grant Beyleveld
title	Nucleolar Relocalization of RBM14 by Influenza A Virus NS1 Protein
title_short	Nucleolar Relocalization of RBM14 by Influenza A Virus NS1 Protein
title_full	Nucleolar Relocalization of RBM14 by Influenza A Virus NS1 Protein
title_fullStr	Nucleolar Relocalization of RBM14 by Influenza A Virus NS1 Protein
title_full_unstemmed	Nucleolar Relocalization of RBM14 by Influenza A Virus NS1 Protein
title_sort	nucleolar relocalization of rbm14 by influenza a virus ns1 protein
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/aef6b66200154570aa11ec6e8e032464
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_version_	1718428025921470464

Nucleolar Relocalization of RBM14 by Influenza A Virus NS1 Protein

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