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Visualization of Double-Stranded RNA Colocalizing With Pattern Recognition Receptors in Arenavirus Infected Cells

An important step in the initiation of the innate immune response to virus infection is the recognition of non-self, viral RNA, including double-stranded RNA (dsRNA), by cytoplasmic pattern recognition receptors (PRRs). For many positive-sense RNA viruses and DNA viruses, the production of viral dsR...

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Autores principales: Mateer, Elizabeth J., Paessler, Slobodan, Huang, Cheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066581/
https://www.ncbi.nlm.nih.gov/pubmed/30087859
http://dx.doi.org/10.3389/fcimb.2018.00251
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author Mateer, Elizabeth J.
Paessler, Slobodan
Huang, Cheng
author_facet Mateer, Elizabeth J.
Paessler, Slobodan
Huang, Cheng
author_sort Mateer, Elizabeth J.
collection PubMed
description An important step in the initiation of the innate immune response to virus infection is the recognition of non-self, viral RNA, including double-stranded RNA (dsRNA), by cytoplasmic pattern recognition receptors (PRRs). For many positive-sense RNA viruses and DNA viruses, the production of viral dsRNA, and the interaction of viral dsRNA and PRRs are well characterized. However, for negative-sense RNA viruses, viral dsRNA was thought to be produced at low to undetectable levels and PRR recognition of viral dsRNA is still largely unclear. In the case of arenaviruses, the nucleocaspid protein (NP) has been identified to contain an exoribonuclease activity that preferentially degrades dsRNA in biochemical studies. Nevertheless, pathogenic New World (NW) arenavirus infections readily induce an interferon (IFN) response in a RIG-I dependent manner, and also activate the dsRNA-dependent Protein Kinase R (PKR). To better understand the innate immune response to pathogenic arenavirus infection, we used a newly identified dsRNA-specific antibody that efficiently detects viral dsRNA in negative-sense RNA virus infected cells. dsRNA was detected in NW arenavirus infected cells colocalizing with virus NP in immunofluorescence assay. Importantly, the dsRNA signals also colocalized with cytoplasmic PRRs, namely, PKR, RIG-I and MDA-5, as well as with the phosphorylated, activated form of PKR in infected cells. Our data clearly demonstrate the PRR recognition of dsRNA and their activation in NW arenavirus infected cells. These findings provide new insights into the interaction between NW arenaviruses and the host innate immune response.
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spelling pubmed-60665812018-08-07 Visualization of Double-Stranded RNA Colocalizing With Pattern Recognition Receptors in Arenavirus Infected Cells Mateer, Elizabeth J. Paessler, Slobodan Huang, Cheng Front Cell Infect Microbiol Cellular and Infection Microbiology An important step in the initiation of the innate immune response to virus infection is the recognition of non-self, viral RNA, including double-stranded RNA (dsRNA), by cytoplasmic pattern recognition receptors (PRRs). For many positive-sense RNA viruses and DNA viruses, the production of viral dsRNA, and the interaction of viral dsRNA and PRRs are well characterized. However, for negative-sense RNA viruses, viral dsRNA was thought to be produced at low to undetectable levels and PRR recognition of viral dsRNA is still largely unclear. In the case of arenaviruses, the nucleocaspid protein (NP) has been identified to contain an exoribonuclease activity that preferentially degrades dsRNA in biochemical studies. Nevertheless, pathogenic New World (NW) arenavirus infections readily induce an interferon (IFN) response in a RIG-I dependent manner, and also activate the dsRNA-dependent Protein Kinase R (PKR). To better understand the innate immune response to pathogenic arenavirus infection, we used a newly identified dsRNA-specific antibody that efficiently detects viral dsRNA in negative-sense RNA virus infected cells. dsRNA was detected in NW arenavirus infected cells colocalizing with virus NP in immunofluorescence assay. Importantly, the dsRNA signals also colocalized with cytoplasmic PRRs, namely, PKR, RIG-I and MDA-5, as well as with the phosphorylated, activated form of PKR in infected cells. Our data clearly demonstrate the PRR recognition of dsRNA and their activation in NW arenavirus infected cells. These findings provide new insights into the interaction between NW arenaviruses and the host innate immune response. Frontiers Media S.A. 2018-07-24 /pmc/articles/PMC6066581/ /pubmed/30087859 http://dx.doi.org/10.3389/fcimb.2018.00251 Text en Copyright © 2018 Mateer, Paessler and Huang. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Mateer, Elizabeth J.
Paessler, Slobodan
Huang, Cheng
Visualization of Double-Stranded RNA Colocalizing With Pattern Recognition Receptors in Arenavirus Infected Cells
title Visualization of Double-Stranded RNA Colocalizing With Pattern Recognition Receptors in Arenavirus Infected Cells
title_full Visualization of Double-Stranded RNA Colocalizing With Pattern Recognition Receptors in Arenavirus Infected Cells
title_fullStr Visualization of Double-Stranded RNA Colocalizing With Pattern Recognition Receptors in Arenavirus Infected Cells
title_full_unstemmed Visualization of Double-Stranded RNA Colocalizing With Pattern Recognition Receptors in Arenavirus Infected Cells
title_short Visualization of Double-Stranded RNA Colocalizing With Pattern Recognition Receptors in Arenavirus Infected Cells
title_sort visualization of double-stranded rna colocalizing with pattern recognition receptors in arenavirus infected cells
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6066581/
https://www.ncbi.nlm.nih.gov/pubmed/30087859
http://dx.doi.org/10.3389/fcimb.2018.00251
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