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A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection
Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This rest...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112549/ https://www.ncbi.nlm.nih.gov/pubmed/24966209 http://dx.doi.org/10.7554/eLife.02910 |
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author | Gammon, Don B Duraffour, Sophie Rozelle, Daniel K Hehnly, Heidi Sharma, Rita Sparks, Michael E West, Cara C Chen, Ying Moresco, James J Andrei, Graciela Connor, John H Conte, Darryl Gundersen-Rindal, Dawn E Marshall, William L Yates, John R Silverman, Neal Mello, Craig C |
author_facet | Gammon, Don B Duraffour, Sophie Rozelle, Daniel K Hehnly, Heidi Sharma, Rita Sparks, Michael E West, Cara C Chen, Ying Moresco, James J Andrei, Graciela Connor, John H Conte, Darryl Gundersen-Rindal, Dawn E Marshall, William L Yates, John R Silverman, Neal Mello, Craig C |
author_sort | Gammon, Don B |
collection | PubMed |
description | Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-κB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems. DOI: http://dx.doi.org/10.7554/eLife.02910.001 |
format | Online Article Text |
id | pubmed-4112549 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-41125492014-08-22 A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection Gammon, Don B Duraffour, Sophie Rozelle, Daniel K Hehnly, Heidi Sharma, Rita Sparks, Michael E West, Cara C Chen, Ying Moresco, James J Andrei, Graciela Connor, John H Conte, Darryl Gundersen-Rindal, Dawn E Marshall, William L Yates, John R Silverman, Neal Mello, Craig C eLife Immunology Virus-host interactions drive a remarkable diversity of immune responses and countermeasures. We found that two RNA viruses with broad host ranges, vesicular stomatitis virus (VSV) and Sindbis virus (SINV), are completely restricted in their replication after entry into Lepidopteran cells. This restriction is overcome when cells are co-infected with vaccinia virus (VACV), a vertebrate DNA virus. Using RNAi screening, we show that Lepidopteran RNAi, Nuclear Factor-κB, and ubiquitin-proteasome pathways restrict RNA virus infection. Surprisingly, a highly conserved, uncharacterized VACV protein, A51R, can partially overcome this virus restriction. We show that A51R is also critical for VACV replication in vertebrate cells and for pathogenesis in mice. Interestingly, A51R colocalizes with, and stabilizes, host microtubules and also associates with ubiquitin. We show that A51R promotes viral protein stability, possibly by preventing ubiquitin-dependent targeting of viral proteins for destruction. Importantly, our studies reveal exciting new opportunities to study virus-host interactions in experimentally-tractable Lepidopteran systems. DOI: http://dx.doi.org/10.7554/eLife.02910.001 eLife Sciences Publications, Ltd 2014-06-25 /pmc/articles/PMC4112549/ /pubmed/24966209 http://dx.doi.org/10.7554/eLife.02910 Text en http://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (http://creativecommons.org/publicdomain/zero/1.0/) . |
spellingShingle | Immunology Gammon, Don B Duraffour, Sophie Rozelle, Daniel K Hehnly, Heidi Sharma, Rita Sparks, Michael E West, Cara C Chen, Ying Moresco, James J Andrei, Graciela Connor, John H Conte, Darryl Gundersen-Rindal, Dawn E Marshall, William L Yates, John R Silverman, Neal Mello, Craig C A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection |
title | A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection |
title_full | A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection |
title_fullStr | A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection |
title_full_unstemmed | A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection |
title_short | A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection |
title_sort | single vertebrate dna virus protein disarms invertebrate immunity to rna virus infection |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4112549/ https://www.ncbi.nlm.nih.gov/pubmed/24966209 http://dx.doi.org/10.7554/eLife.02910 |
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