Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance.
Most individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2018-09-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1007290 |
| _version_ | 1818901972585021440 |
|---|---|
| author | Brad R Rosenberg Marion Depla Catherine A Freije Denis Gaucher Sabrina Mazouz Maude Boisvert Nathalie Bédard Julie Bruneau Charles M Rice Naglaa H Shoukry |
| author_facet | Brad R Rosenberg Marion Depla Catherine A Freije Denis Gaucher Sabrina Mazouz Maude Boisvert Nathalie Bédard Julie Bruneau Charles M Rice Naglaa H Shoukry |
| author_sort | Brad R Rosenberg |
| collection | DOAJ |
| description | Most individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral exposure remain incompletely understood. Employing specimens collected from people who inject drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq and blood transcriptome module (BTM) analysis to characterize immune function in peripheral blood mononuclear cells (PBMC) before, during, and after acute HCV infection resulting in spontaneous resolution. Our results provide a detailed description of innate immune programs active in peripheral blood during acute HCV infection, which include prominent type I interferon and inflammatory signatures. Innate immune gene expression rapidly returns to pre-infection levels upon viral clearance. Comparative analyses using peripheral blood gene expression profiles from other viral and vaccine studies demonstrate similarities in the immune responses to acute HCV and flaviviruses. Of note, both acute dengue virus (DENV) infection and acute HCV infection elicit similar innate antiviral signatures. However, while transient in DENV infection, this signature was sustained for many weeks in the response to HCV. These results represent the first longitudinal transcriptomic characterization of human immune function in PBMC during acute HCV infection and identify several dynamically regulated features of the complex response to natural HCV exposure. |
| first_indexed | 2024-12-19T20:28:15Z |
| format | Article |
| id | doaj.art-b465ecfd4e654bf39641f37a32ae4bfe |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-19T20:28:15Z |
| publishDate | 2018-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-b465ecfd4e654bf39641f37a32ae4bfe2022-12-21T20:06:48ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742018-09-01149e100729010.1371/journal.ppat.1007290Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance.Brad R RosenbergMarion DeplaCatherine A FreijeDenis GaucherSabrina MazouzMaude BoisvertNathalie BédardJulie BruneauCharles M RiceNaglaa H ShoukryMost individuals exposed to hepatitis C virus (HCV) become persistently infected while a minority spontaneously eliminate the virus. Although early immune events influence infection outcome, the cellular composition, molecular effectors, and timeframe of the host response active shortly after viral exposure remain incompletely understood. Employing specimens collected from people who inject drugs (PWID) with high risk of HCV exposure, we utilized RNA-Seq and blood transcriptome module (BTM) analysis to characterize immune function in peripheral blood mononuclear cells (PBMC) before, during, and after acute HCV infection resulting in spontaneous resolution. Our results provide a detailed description of innate immune programs active in peripheral blood during acute HCV infection, which include prominent type I interferon and inflammatory signatures. Innate immune gene expression rapidly returns to pre-infection levels upon viral clearance. Comparative analyses using peripheral blood gene expression profiles from other viral and vaccine studies demonstrate similarities in the immune responses to acute HCV and flaviviruses. Of note, both acute dengue virus (DENV) infection and acute HCV infection elicit similar innate antiviral signatures. However, while transient in DENV infection, this signature was sustained for many weeks in the response to HCV. These results represent the first longitudinal transcriptomic characterization of human immune function in PBMC during acute HCV infection and identify several dynamically regulated features of the complex response to natural HCV exposure.https://doi.org/10.1371/journal.ppat.1007290 |
| spellingShingle | Brad R Rosenberg Marion Depla Catherine A Freije Denis Gaucher Sabrina Mazouz Maude Boisvert Nathalie Bédard Julie Bruneau Charles M Rice Naglaa H Shoukry Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance. PLoS Pathogens |
| title | Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance. |
| title_full | Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance. |
| title_fullStr | Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance. |
| title_full_unstemmed | Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance. |
| title_short | Longitudinal transcriptomic characterization of the immune response to acute hepatitis C virus infection in patients with spontaneous viral clearance. |
| title_sort | longitudinal transcriptomic characterization of the immune response to acute hepatitis c virus infection in patients with spontaneous viral clearance |
| url | https://doi.org/10.1371/journal.ppat.1007290 |
| work_keys_str_mv | AT bradrrosenberg longitudinaltranscriptomiccharacterizationoftheimmuneresponsetoacutehepatitiscvirusinfectioninpatientswithspontaneousviralclearance AT mariondepla longitudinaltranscriptomiccharacterizationoftheimmuneresponsetoacutehepatitiscvirusinfectioninpatientswithspontaneousviralclearance AT catherineafreije longitudinaltranscriptomiccharacterizationoftheimmuneresponsetoacutehepatitiscvirusinfectioninpatientswithspontaneousviralclearance AT denisgaucher longitudinaltranscriptomiccharacterizationoftheimmuneresponsetoacutehepatitiscvirusinfectioninpatientswithspontaneousviralclearance AT sabrinamazouz longitudinaltranscriptomiccharacterizationoftheimmuneresponsetoacutehepatitiscvirusinfectioninpatientswithspontaneousviralclearance AT maudeboisvert longitudinaltranscriptomiccharacterizationoftheimmuneresponsetoacutehepatitiscvirusinfectioninpatientswithspontaneousviralclearance AT nathaliebedard longitudinaltranscriptomiccharacterizationoftheimmuneresponsetoacutehepatitiscvirusinfectioninpatientswithspontaneousviralclearance AT juliebruneau longitudinaltranscriptomiccharacterizationoftheimmuneresponsetoacutehepatitiscvirusinfectioninpatientswithspontaneousviralclearance AT charlesmrice longitudinaltranscriptomiccharacterizationoftheimmuneresponsetoacutehepatitiscvirusinfectioninpatientswithspontaneousviralclearance AT naglaahshoukry longitudinaltranscriptomiccharacterizationoftheimmuneresponsetoacutehepatitiscvirusinfectioninpatientswithspontaneousviralclearance |