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Suppression of RNA interference increases alphavirus replication and virus-associated mortality in Aedes aegypti mosquitoes

BACKGROUND: Arthropod-borne viruses (arboviruses) can persistently infect and cause limited damage to mosquito vectors. RNA interference (RNAi) is a mosquito antiviral response important in restricting RNA virus replication and has been shown to be active against some arboviruses. The goal of this s...

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Autores principales: Cirimotich, Chris M, Scott, Jaclyn C, Phillips, Aaron T, Geiss, Brian J, Olson, Ken E
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660349/
https://www.ncbi.nlm.nih.gov/pubmed/19265532
http://dx.doi.org/10.1186/1471-2180-9-49
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author Cirimotich, Chris M
Scott, Jaclyn C
Phillips, Aaron T
Geiss, Brian J
Olson, Ken E
author_facet Cirimotich, Chris M
Scott, Jaclyn C
Phillips, Aaron T
Geiss, Brian J
Olson, Ken E
author_sort Cirimotich, Chris M
collection PubMed
description BACKGROUND: Arthropod-borne viruses (arboviruses) can persistently infect and cause limited damage to mosquito vectors. RNA interference (RNAi) is a mosquito antiviral response important in restricting RNA virus replication and has been shown to be active against some arboviruses. The goal of this study was to use a recombinant Sindbis virus (SINV; family Togaviridae; genus Alphavirus) that expresses B2 protein of Flock House virus (FHV; family Nodaviridae; genus Alphanodavirus), a protein that inhibits RNAi, to determine the effects of linking arbovirus infection with RNAi inhibition. RESULTS: B2 protein expression from SINV (TE/3'2J) inhibited the accumulation of non-specific small RNAs in Aedes aegypti mosquito cell culture and virus-specific small RNAs both in infected cell culture and Ae. aegypti mosquitoes. More viral genomic and subgenomic RNA accumulated in cells and mosquitoes infected with TE/3'2J virus expressing B2 (TE/3'2J/B2) compared to TE/3'2J and TE/3'2J virus expressing GFP. TE/3'2J/B2 exhibited increased infection rates, dissemination rates, and infectious virus titers in mosquitoes following oral bloodmeal. Following infectious oral bloodmeal, significantly more mosquitoes died when TE/3'2J/B2 was ingested. The virus was 100% lethal following intrathoracic inoculation of multiple mosquito species and lethality was dose-dependent in Ae. aegypti. CONCLUSION: We show that RNAi is active in Ae. aegypti cell culture and that B2 protein inhibits RNAi in mosquito cells when expressed by a recombinant SINV. Also, SINV more efficiently replicates in mosquito cells when RNAi is inhibited. Finally, TE/3'2J/B2 kills mosquitoes in a dose-dependent manner independent of infection route and mosquito species.
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spelling pubmed-26603492009-03-25 Suppression of RNA interference increases alphavirus replication and virus-associated mortality in Aedes aegypti mosquitoes Cirimotich, Chris M Scott, Jaclyn C Phillips, Aaron T Geiss, Brian J Olson, Ken E BMC Microbiol Research article BACKGROUND: Arthropod-borne viruses (arboviruses) can persistently infect and cause limited damage to mosquito vectors. RNA interference (RNAi) is a mosquito antiviral response important in restricting RNA virus replication and has been shown to be active against some arboviruses. The goal of this study was to use a recombinant Sindbis virus (SINV; family Togaviridae; genus Alphavirus) that expresses B2 protein of Flock House virus (FHV; family Nodaviridae; genus Alphanodavirus), a protein that inhibits RNAi, to determine the effects of linking arbovirus infection with RNAi inhibition. RESULTS: B2 protein expression from SINV (TE/3'2J) inhibited the accumulation of non-specific small RNAs in Aedes aegypti mosquito cell culture and virus-specific small RNAs both in infected cell culture and Ae. aegypti mosquitoes. More viral genomic and subgenomic RNA accumulated in cells and mosquitoes infected with TE/3'2J virus expressing B2 (TE/3'2J/B2) compared to TE/3'2J and TE/3'2J virus expressing GFP. TE/3'2J/B2 exhibited increased infection rates, dissemination rates, and infectious virus titers in mosquitoes following oral bloodmeal. Following infectious oral bloodmeal, significantly more mosquitoes died when TE/3'2J/B2 was ingested. The virus was 100% lethal following intrathoracic inoculation of multiple mosquito species and lethality was dose-dependent in Ae. aegypti. CONCLUSION: We show that RNAi is active in Ae. aegypti cell culture and that B2 protein inhibits RNAi in mosquito cells when expressed by a recombinant SINV. Also, SINV more efficiently replicates in mosquito cells when RNAi is inhibited. Finally, TE/3'2J/B2 kills mosquitoes in a dose-dependent manner independent of infection route and mosquito species. BioMed Central 2009-03-05 /pmc/articles/PMC2660349/ /pubmed/19265532 http://dx.doi.org/10.1186/1471-2180-9-49 Text en Copyright ©2009 Cirimotich et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research article
Cirimotich, Chris M
Scott, Jaclyn C
Phillips, Aaron T
Geiss, Brian J
Olson, Ken E
Suppression of RNA interference increases alphavirus replication and virus-associated mortality in Aedes aegypti mosquitoes
title Suppression of RNA interference increases alphavirus replication and virus-associated mortality in Aedes aegypti mosquitoes
title_full Suppression of RNA interference increases alphavirus replication and virus-associated mortality in Aedes aegypti mosquitoes
title_fullStr Suppression of RNA interference increases alphavirus replication and virus-associated mortality in Aedes aegypti mosquitoes
title_full_unstemmed Suppression of RNA interference increases alphavirus replication and virus-associated mortality in Aedes aegypti mosquitoes
title_short Suppression of RNA interference increases alphavirus replication and virus-associated mortality in Aedes aegypti mosquitoes
title_sort suppression of rna interference increases alphavirus replication and virus-associated mortality in aedes aegypti mosquitoes
topic Research article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2660349/
https://www.ncbi.nlm.nih.gov/pubmed/19265532
http://dx.doi.org/10.1186/1471-2180-9-49
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