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Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of the World Health Organization, considering its potential to create a public health emergency and, more importantly, the absence of efficacious drugs and/or vaccines for treatment. The highly pathogenic characteristic...

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Autores principales: Földes, Fanni, Madai, Mónika, Papp, Henrietta, Kemenesi, Gábor, Zana, Brigitta, Geiger, Lili, Gombos, Katalin, Somogyi, Balázs, Bock-Marquette, Ildikó, Jakab, Ferenc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731286/
https://www.ncbi.nlm.nih.gov/pubmed/33297527
http://dx.doi.org/10.3390/molecules25235771
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author Földes, Fanni
Madai, Mónika
Papp, Henrietta
Kemenesi, Gábor
Zana, Brigitta
Geiger, Lili
Gombos, Katalin
Somogyi, Balázs
Bock-Marquette, Ildikó
Jakab, Ferenc
author_facet Földes, Fanni
Madai, Mónika
Papp, Henrietta
Kemenesi, Gábor
Zana, Brigitta
Geiger, Lili
Gombos, Katalin
Somogyi, Balázs
Bock-Marquette, Ildikó
Jakab, Ferenc
author_sort Földes, Fanni
collection PubMed
description Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of the World Health Organization, considering its potential to create a public health emergency and, more importantly, the absence of efficacious drugs and/or vaccines for treatment. The highly pathogenic characteristic of CCHFV restricts research to BSL-4 laboratories, which complicates effective research and developmental strategies. In consideration of antiviral therapies, RNA interference can be used to suppress viral replication by targeting viral genes. RNA interference uses small interfering RNAs (siRNAs) to silence genes. The aim of our study was to design and test siRNAs in vitro that inhibit CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected with CCHFV after transfection with the siRNAs. Following 72 h, nucleic acid from the supernatant was extracted for RT Droplet Digital PCR analysis. Among the investigated siRNAs we identified effective candidates against all three segments of the CCHF genome. Consequently, blocking any segment of CCHFV leads to changes in the virus copy number that indicates an antiviral effect of the siRNAs. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replication in vitro. This promising result can be integrated into future anti-CCHFV therapy developments.
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spelling pubmed-77312862020-12-12 Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro Földes, Fanni Madai, Mónika Papp, Henrietta Kemenesi, Gábor Zana, Brigitta Geiger, Lili Gombos, Katalin Somogyi, Balázs Bock-Marquette, Ildikó Jakab, Ferenc Molecules Article Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of the World Health Organization, considering its potential to create a public health emergency and, more importantly, the absence of efficacious drugs and/or vaccines for treatment. The highly pathogenic characteristic of CCHFV restricts research to BSL-4 laboratories, which complicates effective research and developmental strategies. In consideration of antiviral therapies, RNA interference can be used to suppress viral replication by targeting viral genes. RNA interference uses small interfering RNAs (siRNAs) to silence genes. The aim of our study was to design and test siRNAs in vitro that inhibit CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected with CCHFV after transfection with the siRNAs. Following 72 h, nucleic acid from the supernatant was extracted for RT Droplet Digital PCR analysis. Among the investigated siRNAs we identified effective candidates against all three segments of the CCHF genome. Consequently, blocking any segment of CCHFV leads to changes in the virus copy number that indicates an antiviral effect of the siRNAs. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replication in vitro. This promising result can be integrated into future anti-CCHFV therapy developments. MDPI 2020-12-07 /pmc/articles/PMC7731286/ /pubmed/33297527 http://dx.doi.org/10.3390/molecules25235771 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Földes, Fanni
Madai, Mónika
Papp, Henrietta
Kemenesi, Gábor
Zana, Brigitta
Geiger, Lili
Gombos, Katalin
Somogyi, Balázs
Bock-Marquette, Ildikó
Jakab, Ferenc
Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro
title Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro
title_full Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro
title_fullStr Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro
title_full_unstemmed Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro
title_short Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro
title_sort small interfering rnas are highly effective inhibitors of crimean-congo hemorrhagic fever virus replication in vitro
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731286/
https://www.ncbi.nlm.nih.gov/pubmed/33297527
http://dx.doi.org/10.3390/molecules25235771
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