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Small Interfering RNA Inhibition of Andes Virus Replication

Andes virus (ANDV) is the most common causative agent of hantavirus pulmonary syndrome (HPS) in the Americas, and is the only hantavirus associated with human-to-human transmission. Case fatality rates of ANDV-induced HPS are approximately 40%. There are currently no effective vaccines or antivirals...

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Autores principales: Chiang, Cheng-Feng, Albariňo, Cesar G., Lo, Michael K., Spiropoulou, Christina F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055710/
https://www.ncbi.nlm.nih.gov/pubmed/24924189
http://dx.doi.org/10.1371/journal.pone.0099764
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author Chiang, Cheng-Feng
Albariňo, Cesar G.
Lo, Michael K.
Spiropoulou, Christina F.
author_facet Chiang, Cheng-Feng
Albariňo, Cesar G.
Lo, Michael K.
Spiropoulou, Christina F.
author_sort Chiang, Cheng-Feng
collection PubMed
description Andes virus (ANDV) is the most common causative agent of hantavirus pulmonary syndrome (HPS) in the Americas, and is the only hantavirus associated with human-to-human transmission. Case fatality rates of ANDV-induced HPS are approximately 40%. There are currently no effective vaccines or antivirals against ANDV. Since HPS severity correlates with viral load, we tested small interfering RNA (siRNA) directed against ANDV genes as a potential antiviral strategy. We designed pools of 4 siRNAs targeting each of the ANDV genome segments (S, M, and L), and tested their efficacy in reducing viral replication in vitro. The siRNA pool targeting the S segment reduced viral transcription and replication in Vero-E6 cells more efficiently than those targeting the M and L segments. In contrast, siRNAs targeting the S, M, or L segment were similar in their ability to reduce viral replication in human lung microvascular endothelial cells. Importantly, these siRNAs inhibit ANDV replication even if given after infection. Taken together, our findings indicate that siRNAs targeting the ANDV genome efficiently inhibit ANDV replication, and show promise as a strategy for developing therapeutics against ANDV infection.
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spelling pubmed-40557102014-06-18 Small Interfering RNA Inhibition of Andes Virus Replication Chiang, Cheng-Feng Albariňo, Cesar G. Lo, Michael K. Spiropoulou, Christina F. PLoS One Research Article Andes virus (ANDV) is the most common causative agent of hantavirus pulmonary syndrome (HPS) in the Americas, and is the only hantavirus associated with human-to-human transmission. Case fatality rates of ANDV-induced HPS are approximately 40%. There are currently no effective vaccines or antivirals against ANDV. Since HPS severity correlates with viral load, we tested small interfering RNA (siRNA) directed against ANDV genes as a potential antiviral strategy. We designed pools of 4 siRNAs targeting each of the ANDV genome segments (S, M, and L), and tested their efficacy in reducing viral replication in vitro. The siRNA pool targeting the S segment reduced viral transcription and replication in Vero-E6 cells more efficiently than those targeting the M and L segments. In contrast, siRNAs targeting the S, M, or L segment were similar in their ability to reduce viral replication in human lung microvascular endothelial cells. Importantly, these siRNAs inhibit ANDV replication even if given after infection. Taken together, our findings indicate that siRNAs targeting the ANDV genome efficiently inhibit ANDV replication, and show promise as a strategy for developing therapeutics against ANDV infection. Public Library of Science 2014-06-12 /pmc/articles/PMC4055710/ /pubmed/24924189 http://dx.doi.org/10.1371/journal.pone.0099764 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Chiang, Cheng-Feng
Albariňo, Cesar G.
Lo, Michael K.
Spiropoulou, Christina F.
Small Interfering RNA Inhibition of Andes Virus Replication
title Small Interfering RNA Inhibition of Andes Virus Replication
title_full Small Interfering RNA Inhibition of Andes Virus Replication
title_fullStr Small Interfering RNA Inhibition of Andes Virus Replication
title_full_unstemmed Small Interfering RNA Inhibition of Andes Virus Replication
title_short Small Interfering RNA Inhibition of Andes Virus Replication
title_sort small interfering rna inhibition of andes virus replication
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055710/
https://www.ncbi.nlm.nih.gov/pubmed/24924189
http://dx.doi.org/10.1371/journal.pone.0099764
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