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Genomic HIV RNA Induces Innate Immune Responses through RIG-I-Dependent Sensing of Secondary-Structured RNA
BACKGROUND: Innate immune responses have recently been appreciated to play an important role in the pathogenesis of HIV infection. Whereas inadequate innate immune sensing of HIV during acute infection may contribute to failure to control and eradicate infection, persistent inflammatory responses la...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250430/ https://www.ncbi.nlm.nih.gov/pubmed/22235281 http://dx.doi.org/10.1371/journal.pone.0029291 |
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author | Berg, Randi K. Melchjorsen, Jesper Rintahaka, Johanna Diget, Elisabeth Søby, Stine Horan, Kristy A. Gorelick, Robert J. Matikainen, Sampsa Larsen, Carsten S. Ostergaard, Lars Paludan, Søren R. Mogensen, Trine H. |
author_facet | Berg, Randi K. Melchjorsen, Jesper Rintahaka, Johanna Diget, Elisabeth Søby, Stine Horan, Kristy A. Gorelick, Robert J. Matikainen, Sampsa Larsen, Carsten S. Ostergaard, Lars Paludan, Søren R. Mogensen, Trine H. |
author_sort | Berg, Randi K. |
collection | PubMed |
description | BACKGROUND: Innate immune responses have recently been appreciated to play an important role in the pathogenesis of HIV infection. Whereas inadequate innate immune sensing of HIV during acute infection may contribute to failure to control and eradicate infection, persistent inflammatory responses later during infection contribute in driving chronic immune activation and development of immunodeficiency. However, knowledge on specific HIV PAMPs and cellular PRRs responsible for inducing innate immune responses remains sparse. METHODS/PRINCIPAL FINDINGS: Here we demonstrate a major role for RIG-I and the adaptor protein MAVS in induction of innate immune responses to HIV genomic RNA. We found that secondary structured HIV-derived RNAs induced a response similar to genomic RNA. In primary human peripheral blood mononuclear cells and primary human macrophages, HIV RNA induced expression of IFN-stimulated genes, whereas only low levels of type I IFN and tumor necrosis factor α were produced. Furthermore, secondary structured HIV-derived RNA activated pathways to NF-κB, MAP kinases, and IRF3 and co-localized with peroxisomes, suggesting a role for this organelle in RIG-I-mediated innate immune sensing of HIV RNA. CONCLUSIONS/SIGNIFICANCE: These results establish RIG-I as an innate immune sensor of cytosolic HIV genomic RNA with secondary structure, thereby expanding current knowledge on HIV molecules capable of stimulating the innate immune system. |
format | Online Article Text |
id | pubmed-3250430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32504302012-01-10 Genomic HIV RNA Induces Innate Immune Responses through RIG-I-Dependent Sensing of Secondary-Structured RNA Berg, Randi K. Melchjorsen, Jesper Rintahaka, Johanna Diget, Elisabeth Søby, Stine Horan, Kristy A. Gorelick, Robert J. Matikainen, Sampsa Larsen, Carsten S. Ostergaard, Lars Paludan, Søren R. Mogensen, Trine H. PLoS One Research Article BACKGROUND: Innate immune responses have recently been appreciated to play an important role in the pathogenesis of HIV infection. Whereas inadequate innate immune sensing of HIV during acute infection may contribute to failure to control and eradicate infection, persistent inflammatory responses later during infection contribute in driving chronic immune activation and development of immunodeficiency. However, knowledge on specific HIV PAMPs and cellular PRRs responsible for inducing innate immune responses remains sparse. METHODS/PRINCIPAL FINDINGS: Here we demonstrate a major role for RIG-I and the adaptor protein MAVS in induction of innate immune responses to HIV genomic RNA. We found that secondary structured HIV-derived RNAs induced a response similar to genomic RNA. In primary human peripheral blood mononuclear cells and primary human macrophages, HIV RNA induced expression of IFN-stimulated genes, whereas only low levels of type I IFN and tumor necrosis factor α were produced. Furthermore, secondary structured HIV-derived RNA activated pathways to NF-κB, MAP kinases, and IRF3 and co-localized with peroxisomes, suggesting a role for this organelle in RIG-I-mediated innate immune sensing of HIV RNA. CONCLUSIONS/SIGNIFICANCE: These results establish RIG-I as an innate immune sensor of cytosolic HIV genomic RNA with secondary structure, thereby expanding current knowledge on HIV molecules capable of stimulating the innate immune system. Public Library of Science 2012-01-03 /pmc/articles/PMC3250430/ /pubmed/22235281 http://dx.doi.org/10.1371/journal.pone.0029291 Text en 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. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Berg, Randi K. Melchjorsen, Jesper Rintahaka, Johanna Diget, Elisabeth Søby, Stine Horan, Kristy A. Gorelick, Robert J. Matikainen, Sampsa Larsen, Carsten S. Ostergaard, Lars Paludan, Søren R. Mogensen, Trine H. Genomic HIV RNA Induces Innate Immune Responses through RIG-I-Dependent Sensing of Secondary-Structured RNA |
title | Genomic HIV RNA Induces Innate Immune Responses through RIG-I-Dependent Sensing of Secondary-Structured RNA |
title_full | Genomic HIV RNA Induces Innate Immune Responses through RIG-I-Dependent Sensing of Secondary-Structured RNA |
title_fullStr | Genomic HIV RNA Induces Innate Immune Responses through RIG-I-Dependent Sensing of Secondary-Structured RNA |
title_full_unstemmed | Genomic HIV RNA Induces Innate Immune Responses through RIG-I-Dependent Sensing of Secondary-Structured RNA |
title_short | Genomic HIV RNA Induces Innate Immune Responses through RIG-I-Dependent Sensing of Secondary-Structured RNA |
title_sort | genomic hiv rna induces innate immune responses through rig-i-dependent sensing of secondary-structured rna |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250430/ https://www.ncbi.nlm.nih.gov/pubmed/22235281 http://dx.doi.org/10.1371/journal.pone.0029291 |
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