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Mass spectrometry analysis of gut tissue in acute SIV-infection in rhesus macaques identifies early proteome alterations preceding the interferon inflammatory response
HIV infection damages the gut mucosa leading to chronic immune activation, increased morbidities and mortality, and antiretroviral therapies, do not completely ameliorate mucosal dysfunction. Understanding early molecular changes in acute infection may identify new biomarkers underlying gut dysfunct...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839751/ https://www.ncbi.nlm.nih.gov/pubmed/36639424 http://dx.doi.org/10.1038/s41598-022-27112-y |
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author | Berard, A. R. Hensley-McBain, T. Noël-Romas, L. Birse, K. Abou, M. Westmacott, G. McCorrister, S. Smedley, J. Klatt, Nichole R. Burgener, Adam D. |
author_facet | Berard, A. R. Hensley-McBain, T. Noël-Romas, L. Birse, K. Abou, M. Westmacott, G. McCorrister, S. Smedley, J. Klatt, Nichole R. Burgener, Adam D. |
author_sort | Berard, A. R. |
collection | PubMed |
description | HIV infection damages the gut mucosa leading to chronic immune activation, increased morbidities and mortality, and antiretroviral therapies, do not completely ameliorate mucosal dysfunction. Understanding early molecular changes in acute infection may identify new biomarkers underlying gut dysfunction. Here we utilized a proteomics approach, coupled with flow cytometry, to characterize early molecular and immunological alterations during acute SIV infection in gut tissue of rhesus macaques. Gut tissue biopsies were obtained at 2 times pre-infection and 4 times post-infection from 6 macaques. The tissue proteome was analyzed by mass spectrometry, and immune cell populations in tissue and blood by flow cytometry. Significant proteome changes (p < 0.05) occurred at 3 days post-infection (dpi) (13.0%), 14 dpi (13.7%), 28 dpi (16.9%) and 63 dpi (14.8%). At 3 dpi, proteome changes included cellular structural activity, barrier integrity, and activation of epithelial to mesenchymal transition (EMT) (FDR < 0.0001) prior to the antiviral response at 14 dpi (IFNa/g pathways, p < 0.001). Novel EMT proteomic biomarkers (keratins 2, 6A and 20, collagen 12A1, desmoplakin) and inflammatory biomarkers (PSMB9, FGL2) were associated with early infection and barrier dysfunction. These findings identify new biomarkers preceding inflammation in SIV infection involved with EMT activation. This warrants further investigation of the role of these biomarkers in chronic infection, mucosal inflammation, and disease pathogenesis of HIV. |
format | Online Article Text |
id | pubmed-9839751 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98397512023-01-15 Mass spectrometry analysis of gut tissue in acute SIV-infection in rhesus macaques identifies early proteome alterations preceding the interferon inflammatory response Berard, A. R. Hensley-McBain, T. Noël-Romas, L. Birse, K. Abou, M. Westmacott, G. McCorrister, S. Smedley, J. Klatt, Nichole R. Burgener, Adam D. Sci Rep Article HIV infection damages the gut mucosa leading to chronic immune activation, increased morbidities and mortality, and antiretroviral therapies, do not completely ameliorate mucosal dysfunction. Understanding early molecular changes in acute infection may identify new biomarkers underlying gut dysfunction. Here we utilized a proteomics approach, coupled with flow cytometry, to characterize early molecular and immunological alterations during acute SIV infection in gut tissue of rhesus macaques. Gut tissue biopsies were obtained at 2 times pre-infection and 4 times post-infection from 6 macaques. The tissue proteome was analyzed by mass spectrometry, and immune cell populations in tissue and blood by flow cytometry. Significant proteome changes (p < 0.05) occurred at 3 days post-infection (dpi) (13.0%), 14 dpi (13.7%), 28 dpi (16.9%) and 63 dpi (14.8%). At 3 dpi, proteome changes included cellular structural activity, barrier integrity, and activation of epithelial to mesenchymal transition (EMT) (FDR < 0.0001) prior to the antiviral response at 14 dpi (IFNa/g pathways, p < 0.001). Novel EMT proteomic biomarkers (keratins 2, 6A and 20, collagen 12A1, desmoplakin) and inflammatory biomarkers (PSMB9, FGL2) were associated with early infection and barrier dysfunction. These findings identify new biomarkers preceding inflammation in SIV infection involved with EMT activation. This warrants further investigation of the role of these biomarkers in chronic infection, mucosal inflammation, and disease pathogenesis of HIV. Nature Publishing Group UK 2023-01-13 /pmc/articles/PMC9839751/ /pubmed/36639424 http://dx.doi.org/10.1038/s41598-022-27112-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Berard, A. R. Hensley-McBain, T. Noël-Romas, L. Birse, K. Abou, M. Westmacott, G. McCorrister, S. Smedley, J. Klatt, Nichole R. Burgener, Adam D. Mass spectrometry analysis of gut tissue in acute SIV-infection in rhesus macaques identifies early proteome alterations preceding the interferon inflammatory response |
title | Mass spectrometry analysis of gut tissue in acute SIV-infection in rhesus macaques identifies early proteome alterations preceding the interferon inflammatory response |
title_full | Mass spectrometry analysis of gut tissue in acute SIV-infection in rhesus macaques identifies early proteome alterations preceding the interferon inflammatory response |
title_fullStr | Mass spectrometry analysis of gut tissue in acute SIV-infection in rhesus macaques identifies early proteome alterations preceding the interferon inflammatory response |
title_full_unstemmed | Mass spectrometry analysis of gut tissue in acute SIV-infection in rhesus macaques identifies early proteome alterations preceding the interferon inflammatory response |
title_short | Mass spectrometry analysis of gut tissue in acute SIV-infection in rhesus macaques identifies early proteome alterations preceding the interferon inflammatory response |
title_sort | mass spectrometry analysis of gut tissue in acute siv-infection in rhesus macaques identifies early proteome alterations preceding the interferon inflammatory response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9839751/ https://www.ncbi.nlm.nih.gov/pubmed/36639424 http://dx.doi.org/10.1038/s41598-022-27112-y |
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