A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections

Introduction: Within the inflammatory immune response to viral infection, the distribution and cell type-specific profiles of immune cell populations and the immune-mediated viral clearance pathways vary according to the specific virus. Uncovering the immunological similarities and differences betwe...

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Main Authors: Tony Pan, Guoshuai Cao, Erting Tang, Yu Zhao, Pablo Penaloza-MacMaster, Yun Fang, Jun Huang
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2023.1105673/full
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author Tony Pan
Guoshuai Cao
Erting Tang
Yu Zhao
Pablo Penaloza-MacMaster
Yun Fang
Jun Huang
author_facet Tony Pan
Guoshuai Cao
Erting Tang
Yu Zhao
Pablo Penaloza-MacMaster
Yun Fang
Jun Huang
author_sort Tony Pan
collection DOAJ
description Introduction: Within the inflammatory immune response to viral infection, the distribution and cell type-specific profiles of immune cell populations and the immune-mediated viral clearance pathways vary according to the specific virus. Uncovering the immunological similarities and differences between viral infections is critical to understanding disease progression and developing effective vaccines and therapies. Insight into COVID-19 disease progression has been bolstered by the integration of single-cell (sc)RNA-seq data from COVID-19 patients with data from related viruses to compare immune responses. Expanding this concept, we propose that a high-resolution, systematic comparison between immune cells from SARS-CoV-2 infection and an inflammatory infectious disease with a different pathophysiology will provide a more comprehensive picture of the viral clearance pathways that underscore immunological and clinical differences between infections.Methods: Using a novel consensus single-cell annotation method, we integrate previously published scRNA-seq data from 111,566 single PBMCs from 7 COVID-19, 10 HIV-1+, and 3 healthy patients into a unified cellular atlas. We compare in detail the phenotypic features and regulatory pathways in the major immune cell clusters.Results: While immune cells in both COVID-19 and HIV-1+ cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activity, and downregulated mitophagy.Discussion: Our results indicate that differential IFN-I signaling regulates the distinct immune responses in the two diseases, revealing insight into fundamental disease biology and potential therapeutic candidates.
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spelling doaj.art-39c46221630844139b82af54c67273112023-03-13T05:54:08ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-03-011410.3389/fgene.2023.11056731105673A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infectionsTony Pan0Guoshuai Cao1Erting Tang2Yu Zhao3Pablo Penaloza-MacMaster4Yun Fang5Jun Huang6Pritzker School of Molecular Engineering, University of Chicago, Chicago, IL, United StatesPritzker School of Molecular Engineering, University of Chicago, Chicago, IL, United StatesPritzker School of Molecular Engineering, University of Chicago, Chicago, IL, United StatesPritzker School of Molecular Engineering, University of Chicago, Chicago, IL, United StatesDepartment of Microbiology-Immunology, Northwestern University, Chicago, IL, United StatesBiological Sciences Division, University of Chicago, Chicago, IL, United StatesPritzker School of Molecular Engineering, University of Chicago, Chicago, IL, United StatesIntroduction: Within the inflammatory immune response to viral infection, the distribution and cell type-specific profiles of immune cell populations and the immune-mediated viral clearance pathways vary according to the specific virus. Uncovering the immunological similarities and differences between viral infections is critical to understanding disease progression and developing effective vaccines and therapies. Insight into COVID-19 disease progression has been bolstered by the integration of single-cell (sc)RNA-seq data from COVID-19 patients with data from related viruses to compare immune responses. Expanding this concept, we propose that a high-resolution, systematic comparison between immune cells from SARS-CoV-2 infection and an inflammatory infectious disease with a different pathophysiology will provide a more comprehensive picture of the viral clearance pathways that underscore immunological and clinical differences between infections.Methods: Using a novel consensus single-cell annotation method, we integrate previously published scRNA-seq data from 111,566 single PBMCs from 7 COVID-19, 10 HIV-1+, and 3 healthy patients into a unified cellular atlas. We compare in detail the phenotypic features and regulatory pathways in the major immune cell clusters.Results: While immune cells in both COVID-19 and HIV-1+ cohorts show shared inflammation and disrupted mitochondrial function, COVID-19 patients exhibit stronger humoral immunity, broader IFN-I signaling, elevated Rho GTPase and mTOR pathway activity, and downregulated mitophagy.Discussion: Our results indicate that differential IFN-I signaling regulates the distinct immune responses in the two diseases, revealing insight into fundamental disease biology and potential therapeutic candidates.https://www.frontiersin.org/articles/10.3389/fgene.2023.1105673/fullHIVSingle-cell RNA sequencingSARS-CoV-2type 1 interferoninflammationmetabolic signaling
spellingShingle Tony Pan
Guoshuai Cao
Erting Tang
Yu Zhao
Pablo Penaloza-MacMaster
Yun Fang
Jun Huang
A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections
Frontiers in Genetics
HIV
Single-cell RNA sequencing
SARS-CoV-2
type 1 interferon
inflammation
metabolic signaling
title A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections
title_full A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections
title_fullStr A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections
title_full_unstemmed A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections
title_short A single-cell atlas reveals shared and distinct immune responses and metabolic profiles in SARS-CoV-2 and HIV-1 infections
title_sort single cell atlas reveals shared and distinct immune responses and metabolic profiles in sars cov 2 and hiv 1 infections
topic HIV
Single-cell RNA sequencing
SARS-CoV-2
type 1 interferon
inflammation
metabolic signaling
url https://www.frontiersin.org/articles/10.3389/fgene.2023.1105673/full
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