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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Bibliographic Details
Published in:	PLoS pathogens Vol. 16; no. 10; p. e1008868
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 13-10-2020 Public Library of Science (PLoS)
Subjects:	Accuracy Aging Anti-Retroviral Agents - therapeutic use Antibodies Antigens Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Bioengineering Biological markers Biology and Life Sciences Biomarkers Biomarkers - blood Care and treatment Cell receptors Development and progression Engineering schools Fc receptors Genetic aspects Health aspects HIV HIV Antibodies - blood HIV Antibodies - immunology HIV infection HIV Infections - blood HIV Infections - drug therapy HIV Infections - immunology HIV-1 - drug effects HIV-1 - immunology Human immunodeficiency virus Humans Identification and classification Immune response Immunology Infections Inflammation Life sciences Lymphocytes Medicine and Health Sciences Monitoring Physical Sciences Polysaccharides Protein binding Telemedicine Viral Load - drug effects Viral Load - immunology Virus Latency - drug effects Virus Latency - immunology Virus Replication Viruses United States United States > US San Francisco California
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 The authors affiliated with Gilead Sciences Inc are current employees of the company and may own company stock. This does not alter our adherence to all PLOS Pathogens policies on sharing data and materials. Current address: Center for Systems Immunology, Departments of Immunology and Computational & Systems Biology, University of Pittsburgh School of Medicine, Pittsurgh PA 15213, United States of America
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1008868