Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.

West Nile (WN) and St. Louis encephalitis (SLE) viruses can cause fatal neurological infection and currently there is neither a specific treatment nor an approved vaccine for these infections. In our earlier studies, we have reported that siRNAs can be developed as broad-spectrum antivirals for the...

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Autores principales:	Chunting Ye, Sojan Abraham, Haoquan Wu, Premlata Shankar, N Manjunath
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e408482614e4fdf9cc1f803e1ad1616
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spelling	oai:doaj.org-article:9e408482614e4fdf9cc1f803e1ad16162021-11-18T06:57:16ZSilencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.1932-620310.1371/journal.pone.0017889https://doaj.org/article/9e408482614e4fdf9cc1f803e1ad16162011-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21423625/?tool=EBIhttps://doaj.org/toc/1932-6203West Nile (WN) and St. Louis encephalitis (SLE) viruses can cause fatal neurological infection and currently there is neither a specific treatment nor an approved vaccine for these infections. In our earlier studies, we have reported that siRNAs can be developed as broad-spectrum antivirals for the treatment of infection caused by related viruses and that a small peptide called RVG-9R can deliver siRNA to neuronal cells as well as macrophages. To increase the repertoire of broad-spectrum antiflaviviral siRNAs, we screened 25 siRNAs targeting conserved regions in the viral genome. Five siRNAs were found to inhibit both WNV and SLE replication in vitro reflecting broad-spectrum antiviral activity and one of these was also validated in vivo. In addition, we also show that RVG-9R delivers siRNA to macrophages and dendritic cells, resulting in effective suppression of virus replication. Mice were challenged intraperitoneally (i.p.) with West Nile virus (WNV) and treated i.v. with siRNA/peptide complex. The peritoneal macrophages isolated on day 3 post infection were isolated and transferred to new hosts. Mice receiving macrophages from the anti-viral siRNA treated mice failed to develop any disease while the control mice transferred with irrelevant siRNA treated mice all died of encephalitis. These studies suggest that early suppression of viral replication in macrophages and dendritic cells by RVG-9R-mediated siRNA delivery is key to preventing the development of a fatal neurological disease.Chunting YeSojan AbrahamHaoquan WuPremlata ShankarN ManjunathPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 3, p e17889 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chunting Ye Sojan Abraham Haoquan Wu Premlata Shankar N Manjunath Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.
description	West Nile (WN) and St. Louis encephalitis (SLE) viruses can cause fatal neurological infection and currently there is neither a specific treatment nor an approved vaccine for these infections. In our earlier studies, we have reported that siRNAs can be developed as broad-spectrum antivirals for the treatment of infection caused by related viruses and that a small peptide called RVG-9R can deliver siRNA to neuronal cells as well as macrophages. To increase the repertoire of broad-spectrum antiflaviviral siRNAs, we screened 25 siRNAs targeting conserved regions in the viral genome. Five siRNAs were found to inhibit both WNV and SLE replication in vitro reflecting broad-spectrum antiviral activity and one of these was also validated in vivo. In addition, we also show that RVG-9R delivers siRNA to macrophages and dendritic cells, resulting in effective suppression of virus replication. Mice were challenged intraperitoneally (i.p.) with West Nile virus (WNV) and treated i.v. with siRNA/peptide complex. The peritoneal macrophages isolated on day 3 post infection were isolated and transferred to new hosts. Mice receiving macrophages from the anti-viral siRNA treated mice failed to develop any disease while the control mice transferred with irrelevant siRNA treated mice all died of encephalitis. These studies suggest that early suppression of viral replication in macrophages and dendritic cells by RVG-9R-mediated siRNA delivery is key to preventing the development of a fatal neurological disease.
format	article
author	Chunting Ye Sojan Abraham Haoquan Wu Premlata Shankar N Manjunath
author_facet	Chunting Ye Sojan Abraham Haoquan Wu Premlata Shankar N Manjunath
author_sort	Chunting Ye
title	Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.
title_short	Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.
title_full	Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.
title_fullStr	Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.
title_full_unstemmed	Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.
title_sort	silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/9e408482614e4fdf9cc1f803e1ad1616
work_keys_str_mv	AT chuntingye silencingearlyviralreplicationinmacrophagesanddendriticcellseffectivelysuppressesflavivirusencephalitis AT sojanabraham silencingearlyviralreplicationinmacrophagesanddendriticcellseffectivelysuppressesflavivirusencephalitis AT haoquanwu silencingearlyviralreplicationinmacrophagesanddendriticcellseffectivelysuppressesflavivirusencephalitis AT premlatashankar silencingearlyviralreplicationinmacrophagesanddendriticcellseffectivelysuppressesflavivirusencephalitis AT nmanjunath silencingearlyviralreplicationinmacrophagesanddendriticcellseffectivelysuppressesflavivirusencephalitis
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Silencing early viral replication in macrophages and dendritic cells effectively suppresses flavivirus encephalitis.

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