Cargando…
Cell type- and replication stage-specific influenza virus responses in vivo
Influenza A viruses (IAVs) remain a significant global health burden. Activation of the innate immune response is important for controlling early virus replication and spread. It is unclear how early IAV replication events contribute to immune detection. Additionally, while many cell types in the lu...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447048/ https://www.ncbi.nlm.nih.gov/pubmed/32790753 http://dx.doi.org/10.1371/journal.ppat.1008760 |
_version_ | 1783574234527694848 |
---|---|
author | Fay, Elizabeth J. Aron, Stephanie L. Macchietto, Marissa G. Markman, Matthew W. Esser-Nobis, Katharina Gale, Michael Shen, Steven Langlois, Ryan A. |
author_facet | Fay, Elizabeth J. Aron, Stephanie L. Macchietto, Marissa G. Markman, Matthew W. Esser-Nobis, Katharina Gale, Michael Shen, Steven Langlois, Ryan A. |
author_sort | Fay, Elizabeth J. |
collection | PubMed |
description | Influenza A viruses (IAVs) remain a significant global health burden. Activation of the innate immune response is important for controlling early virus replication and spread. It is unclear how early IAV replication events contribute to immune detection. Additionally, while many cell types in the lung can be infected, it is not known if all cell types contribute equally to establish the antiviral state in the host. Here, we use single-cycle influenza A viruses (scIAVs) to characterize the early immune response to IAV in vitro and in vivo. We found that the magnitude of virus replication contributes to antiviral gene expression within infected cells prior to the induction of a global response. We also developed a scIAV that is only capable of undergoing primary transcription, the earliest stage of virus replication. Using this tool, we uncovered replication stage-specific responses in vitro and in vivo. Using several innate immune receptor knockout cell lines, we identify RIG-I as the predominant antiviral detector of primary virus transcription and amplified replication in vitro. Through a Cre-inducible reporter mouse, we used scIAVs expressing Cre-recombinase to characterize cell type-specific responses in vivo. Individual cell types upregulate unique sets of antiviral genes in response to both primary virus transcription and amplified replication. We also identified antiviral genes that are only upregulated in response to direct infection. Altogether, these data offer insight into the early mechanisms of antiviral gene activation during influenza A infection. |
format | Online Article Text |
id | pubmed-7447048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-74470482020-08-31 Cell type- and replication stage-specific influenza virus responses in vivo Fay, Elizabeth J. Aron, Stephanie L. Macchietto, Marissa G. Markman, Matthew W. Esser-Nobis, Katharina Gale, Michael Shen, Steven Langlois, Ryan A. PLoS Pathog Research Article Influenza A viruses (IAVs) remain a significant global health burden. Activation of the innate immune response is important for controlling early virus replication and spread. It is unclear how early IAV replication events contribute to immune detection. Additionally, while many cell types in the lung can be infected, it is not known if all cell types contribute equally to establish the antiviral state in the host. Here, we use single-cycle influenza A viruses (scIAVs) to characterize the early immune response to IAV in vitro and in vivo. We found that the magnitude of virus replication contributes to antiviral gene expression within infected cells prior to the induction of a global response. We also developed a scIAV that is only capable of undergoing primary transcription, the earliest stage of virus replication. Using this tool, we uncovered replication stage-specific responses in vitro and in vivo. Using several innate immune receptor knockout cell lines, we identify RIG-I as the predominant antiviral detector of primary virus transcription and amplified replication in vitro. Through a Cre-inducible reporter mouse, we used scIAVs expressing Cre-recombinase to characterize cell type-specific responses in vivo. Individual cell types upregulate unique sets of antiviral genes in response to both primary virus transcription and amplified replication. We also identified antiviral genes that are only upregulated in response to direct infection. Altogether, these data offer insight into the early mechanisms of antiviral gene activation during influenza A infection. Public Library of Science 2020-08-13 /pmc/articles/PMC7447048/ /pubmed/32790753 http://dx.doi.org/10.1371/journal.ppat.1008760 Text en © 2020 Fay et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Fay, Elizabeth J. Aron, Stephanie L. Macchietto, Marissa G. Markman, Matthew W. Esser-Nobis, Katharina Gale, Michael Shen, Steven Langlois, Ryan A. Cell type- and replication stage-specific influenza virus responses in vivo |
title | Cell type- and replication stage-specific influenza virus responses in vivo |
title_full | Cell type- and replication stage-specific influenza virus responses in vivo |
title_fullStr | Cell type- and replication stage-specific influenza virus responses in vivo |
title_full_unstemmed | Cell type- and replication stage-specific influenza virus responses in vivo |
title_short | Cell type- and replication stage-specific influenza virus responses in vivo |
title_sort | cell type- and replication stage-specific influenza virus responses in vivo |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447048/ https://www.ncbi.nlm.nih.gov/pubmed/32790753 http://dx.doi.org/10.1371/journal.ppat.1008760 |
work_keys_str_mv | AT fayelizabethj celltypeandreplicationstagespecificinfluenzavirusresponsesinvivo AT aronstephaniel celltypeandreplicationstagespecificinfluenzavirusresponsesinvivo AT macchiettomarissag celltypeandreplicationstagespecificinfluenzavirusresponsesinvivo AT markmanmattheww celltypeandreplicationstagespecificinfluenzavirusresponsesinvivo AT essernobiskatharina celltypeandreplicationstagespecificinfluenzavirusresponsesinvivo AT galemichael celltypeandreplicationstagespecificinfluenzavirusresponsesinvivo AT shensteven celltypeandreplicationstagespecificinfluenzavirusresponsesinvivo AT langloisryana celltypeandreplicationstagespecificinfluenzavirusresponsesinvivo |