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Mining for humoral correlates of HIV control and latent reservoir size

While antiretroviral therapy (ART) has effectively revolutionized HIV care, the virus is never fully eliminated. Instead, immune dysfunction, driven by persistent non-specific immune activation, ensues and progressively leads to premature immunologic aging. Current biomarkers monitoring immunologic...

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Autores principales: Das, Jishnu, Devadhasan, Anush, Linde, Caitlyn, Broge, Tom, Sassic, Jessica, Mangano, Max, O'Keefe, Sean, Suscovich, Todd, Streeck, Hendrik, Irrinki, Alivelu, Pohlmeyer, Chris, Min-Oo, Gundula, Lin, Shu, Weiner, Joshua A., Cihlar, Thomas, Ackerman, Margaret E., Julg, Boris, Deeks, Steven, Lauffenburger, Douglas A., Alter, Galit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553335/
https://www.ncbi.nlm.nih.gov/pubmed/33048992
http://dx.doi.org/10.1371/journal.ppat.1008868
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author Das, Jishnu
Devadhasan, Anush
Linde, Caitlyn
Broge, Tom
Sassic, Jessica
Mangano, Max
O'Keefe, Sean
Suscovich, Todd
Streeck, Hendrik
Irrinki, Alivelu
Pohlmeyer, Chris
Min-Oo, Gundula
Lin, Shu
Weiner, Joshua A.
Cihlar, Thomas
Ackerman, Margaret E.
Julg, Boris
Deeks, Steven
Lauffenburger, Douglas A.
Alter, Galit
author_facet Das, Jishnu
Devadhasan, Anush
Linde, Caitlyn
Broge, Tom
Sassic, Jessica
Mangano, Max
O'Keefe, Sean
Suscovich, Todd
Streeck, Hendrik
Irrinki, Alivelu
Pohlmeyer, Chris
Min-Oo, Gundula
Lin, Shu
Weiner, Joshua A.
Cihlar, Thomas
Ackerman, Margaret E.
Julg, Boris
Deeks, Steven
Lauffenburger, Douglas A.
Alter, Galit
author_sort Das, Jishnu
collection PubMed
description While antiretroviral therapy (ART) has effectively revolutionized HIV care, the virus is never fully eliminated. Instead, immune dysfunction, driven by persistent non-specific immune activation, ensues and progressively leads to premature immunologic aging. Current biomarkers monitoring immunologic changes encompass generic inflammatory biomarkers, that may also change with other infections or disease states, precluding the antigen-specific monitoring of HIV-infection associated changes in disease. Given our growing appreciation of the significant changes in qualitative and quantitative properties of disease-specific antibodies in HIV infection, we used a systems approach to explore humoral profiles associated with HIV control. We found that HIV-specific antibody profiles diverge by spontaneous control of HIV, treatment status, viral load and reservoir size. Specifically, HIV-specific antibody profiles representative of changes in viral load were largely quantitative, reflected by differential HIV-specific antibody levels and Fc-receptor binding. Conversely, HIV-specific antibody features that tracked with reservoir size exhibited a combination of quantitative and qualitative changes marked by more distinct subclass selection profiles and unique HIV-specific Fc-glycans. Our analyses suggest that HIV-specific antibody Fc-profiles provide antigen-specific resolution on both cell free and cell-associated viral loads, pointing to potentially novel biomarkers to monitor reservoir activity.
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spelling pubmed-75533352020-10-21 Mining for humoral correlates of HIV control and latent reservoir size Das, Jishnu Devadhasan, Anush Linde, Caitlyn Broge, Tom Sassic, Jessica Mangano, Max O'Keefe, Sean Suscovich, Todd Streeck, Hendrik Irrinki, Alivelu Pohlmeyer, Chris Min-Oo, Gundula Lin, Shu Weiner, Joshua A. Cihlar, Thomas Ackerman, Margaret E. Julg, Boris Deeks, Steven Lauffenburger, Douglas A. Alter, Galit PLoS Pathog Research Article While antiretroviral therapy (ART) has effectively revolutionized HIV care, the virus is never fully eliminated. Instead, immune dysfunction, driven by persistent non-specific immune activation, ensues and progressively leads to premature immunologic aging. Current biomarkers monitoring immunologic changes encompass generic inflammatory biomarkers, that may also change with other infections or disease states, precluding the antigen-specific monitoring of HIV-infection associated changes in disease. Given our growing appreciation of the significant changes in qualitative and quantitative properties of disease-specific antibodies in HIV infection, we used a systems approach to explore humoral profiles associated with HIV control. We found that HIV-specific antibody profiles diverge by spontaneous control of HIV, treatment status, viral load and reservoir size. Specifically, HIV-specific antibody profiles representative of changes in viral load were largely quantitative, reflected by differential HIV-specific antibody levels and Fc-receptor binding. Conversely, HIV-specific antibody features that tracked with reservoir size exhibited a combination of quantitative and qualitative changes marked by more distinct subclass selection profiles and unique HIV-specific Fc-glycans. Our analyses suggest that HIV-specific antibody Fc-profiles provide antigen-specific resolution on both cell free and cell-associated viral loads, pointing to potentially novel biomarkers to monitor reservoir activity. Public Library of Science 2020-10-13 /pmc/articles/PMC7553335/ /pubmed/33048992 http://dx.doi.org/10.1371/journal.ppat.1008868 Text en © 2020 Das 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
Das, Jishnu
Devadhasan, Anush
Linde, Caitlyn
Broge, Tom
Sassic, Jessica
Mangano, Max
O'Keefe, Sean
Suscovich, Todd
Streeck, Hendrik
Irrinki, Alivelu
Pohlmeyer, Chris
Min-Oo, Gundula
Lin, Shu
Weiner, Joshua A.
Cihlar, Thomas
Ackerman, Margaret E.
Julg, Boris
Deeks, Steven
Lauffenburger, Douglas A.
Alter, Galit
Mining for humoral correlates of HIV control and latent reservoir size
title Mining for humoral correlates of HIV control and latent reservoir size
title_full Mining for humoral correlates of HIV control and latent reservoir size
title_fullStr Mining for humoral correlates of HIV control and latent reservoir size
title_full_unstemmed Mining for humoral correlates of HIV control and latent reservoir size
title_short Mining for humoral correlates of HIV control and latent reservoir size
title_sort mining for humoral correlates of hiv control and latent reservoir size
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553335/
https://www.ncbi.nlm.nih.gov/pubmed/33048992
http://dx.doi.org/10.1371/journal.ppat.1008868
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