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Functional HIV-1/HCV cross-reactive antibodies isolated from a chronically co-infected donor.

ABSTRACT: Despite prolific efforts to characterize the antibody response to human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) mono-infections, the response to chronic co-infection with these two ever-evolving viruses is poorly understood. Here, we investigate the antibody repertoire of a chronically HIV-1/HCV co-infected individual using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq). We identify five HIV-1/HCV cross-reactive antibodies demonstrating binding and functional cross-reactivity between HIV-1 and HCV envelope glycoproteins. All five antibodies show exceptional HCV neutralization breadth and effector functions against both HIV-1 and HCV. One antibody, mAb688, also cross-reacts with influenza and coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We examine the development of these antibodies using next-generation sequencing analysis and lineage tracing and find that somatic hypermutation established and enhanced this reactivity. These antibodies provide a potential future direction for therapeutic and vaccine development against current and emerging infectious diseases. More broadly, chronic co-infection represents a complex immunological challenge that can provide insights into the fundamental rules that underly antibody-antigen specificity.

SUBMITTER: Pilewski KA

PROVIDER: S-EPMC10372200 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Functional HIV-1/HCV cross-reactive antibodies isolated from a chronically co-infected donor.

Pilewski Kelsey A KA Wall Steven S Richardson Simone I SI Manamela Nelia P NP Clark Kaitlyn K Hermanus Tandile T Binshtein Elad E Venkat Rohit R Sautto Giuseppe A GA Kramer Kevin J KJ Shiakolas Andrea R AR Setliff Ian I Salas Jordan J Mapengo Rutendo E RE Suryadevara Naveen N Brannon John R JR Beebout Connor J CJ Parks Rob R Raju Nagarajan N Frumento Nicole N Walker Lauren M LM Fechter Emilee Friedman EF Qin Juliana S JS Murji Amyn A AA Janowska Katarzyna K Thakur Bhishem B Lindenberger Jared J May Aaron J AJ Huang Xiao X Sammour Salam S Acharya Priyamvada P Carnahan Robert H RH Ross Ted M TM Haynes Barton F BF Hadjifrangiskou Maria M Crowe James E JE Bailey Justin R JR Kalams Spyros S Morris Lynn L Georgiev Ivelin S IS

Cell reports 20230127 2

Despite prolific efforts to characterize the antibody response to human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) mono-infections, the response to chronic co-infection with these two ever-evolving viruses is poorly understood. Here, we investigate the antibody repertoire of a chronically HIV-1/HCV co-infected individual using linking B cell receptor to antigen specificity through sequencing (LIBRA-seq). We identify five HIV-1/HCV cross-reactive antibodies demonstrating bi ...[more]

PMID: 36708513

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Project description:BackgroundImmune biomarkers are implicated in HCV treatment response, fibrosis, and accelerated pathogenesis of comorbidities, though only D-dimer and C-reactive protein have been consistently studied. Few studies have evaluated HIV/HCV co-infection, and little longitudinal data exists describing a broader antiviral cytokine response.MethodsFifty immune biomarkers were analyzed at baseline (BL) and HCV end of treatment follow-up(FU) time point using the Luminex 50-plex assay in plasma samples from 15 HCV-cleared, 24 HCV mono- and 49 HIV/HCV co-infected patients receiving antiretroviral treatment, who either did or did not receive pegylated-interferon/ribavirin HCV treatment. Biomarker levels were compared among spontaneous clearance patients, mono- and co-infected, untreated and HCV-treated, and sustained virologic responders (SVR) and non-responders (NR) at BL and FU using nonparametric analyses. A Bonferroni correction, adjusting for tests of 50 biomarkers, was used to reduce Type I error.ResultsCompared to HCV patients at BL, HIV/HCV patients had 22 significantly higher and 4 significantly lower biomarker levels, following correction for multiple testing. There were no significantly different BL levels when comparing SVR and NR in mono- or co-infected patients; however, FU levels changed considerably in co-infected patients, with seven becoming significantly higher and eight becoming significantly lower in SVR patients. Longitudinally between BL and FU, 13 markers significantly changed in co-infected SVR patients, while none significantly changed in co-infected NR patients. There were also no significant changes in longitudinal analyses of mono-infected patients achieving SVR or mono-infected and co-infected groups deferring treatment.ConclusionsClear differences exist in pattern and quantity of plasma immune biomarkers among HCV mono-infected, HIV/HCV co-infected, and HCV-cleared patients; and with SVR in co-infected patients treated for HCV. Though >90% of patients were male and co-infected had a larger percentage of African American patients, our findings may have implications for better understanding HCV pathogenesis, treatment outcomes, and future therapeutic targets.

Dataset Information

Functional HIV-1/HCV cross-reactive antibodies isolated from a chronically co-infected donor.

Publications

Functional HIV-1/HCV cross-reactive antibodies isolated from a chronically co-infected donor.

Similar Datasets

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