Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes.

Chronic infection with HCV is manifested by dysregulation of innate immune responses and impaired T cell function at multiple levels. These changes may impact susceptibility to other infections, responsiveness to antiviral therapies, vaccine responsiveness, and development of complications such as h...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Matthew A Burchill, Matthew P Salomon, Lucy Golden-Mason, Amanda Wieland, Ana C Maretti-Mira, Michael Gale, Hugo R Rosen
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/4b3c7cb12eb447ffbe8a00b8895b480b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4b3c7cb12eb447ffbe8a00b8895b480b
record_format	dspace
spelling	oai:doaj.org-article:4b3c7cb12eb447ffbe8a00b8895b480b2021-12-02T20:00:24ZSingle-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes.1553-73661553-737410.1371/journal.ppat.1009799https://doaj.org/article/4b3c7cb12eb447ffbe8a00b8895b480b2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009799https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Chronic infection with HCV is manifested by dysregulation of innate immune responses and impaired T cell function at multiple levels. These changes may impact susceptibility to other infections, responsiveness to antiviral therapies, vaccine responsiveness, and development of complications such as hepatocellular carcinoma. Highly effective direct-acting antiviral (DAA) therapy has revolutionized the management of chronic HCV, with expected cure rates exceeding 95%. DAA treatment represents a unique opportunity to investigate to what extent elimination of viral replication and chronic antigen stimulation can restore immunologic phenotype. In this study we interrogated the global transcriptional profile of isolated peripheral blood T cells before, during and after IFN-free DAA therapy using single-cell mRNA sequencing. Our results demonstrate that T cells mapped at single-cell resolution have dramatic transcriptomic changes early after initiation of DAA and many of these changes are sustained after completion of DAA therapy. Specifically, we see a significant reduction in transcripts associated with innate immune activation and interferon signaling such as ISG15, ISG20, IFIT3, OAS and MX1 in many different T cell subsets. Furthermore, we find an early upregulation of a gene involved in suppression of immune activation, DUSP1, in circulating T cells. Conclusion: This study provides the first in-depth transcriptomic analysis at the single-cell level of patients undergoing DAA therapy, demonstrating that IFN-free antiviral therapy in chronic HCV infection induces hitherto unrecognized shifts in innate immune and interferon signaling within T cell populations early, during, and long-term after treatment. The present study provides a rich data source to explore the effects of DAA treatment on bulk T cells.Matthew A BurchillMatthew P SalomonLucy Golden-MasonAmanda WielandAna C Maretti-MiraMichael GaleHugo R RosenPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009799 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Matthew A Burchill Matthew P Salomon Lucy Golden-Mason Amanda Wieland Ana C Maretti-Mira Michael Gale Hugo R Rosen Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes.
description	Chronic infection with HCV is manifested by dysregulation of innate immune responses and impaired T cell function at multiple levels. These changes may impact susceptibility to other infections, responsiveness to antiviral therapies, vaccine responsiveness, and development of complications such as hepatocellular carcinoma. Highly effective direct-acting antiviral (DAA) therapy has revolutionized the management of chronic HCV, with expected cure rates exceeding 95%. DAA treatment represents a unique opportunity to investigate to what extent elimination of viral replication and chronic antigen stimulation can restore immunologic phenotype. In this study we interrogated the global transcriptional profile of isolated peripheral blood T cells before, during and after IFN-free DAA therapy using single-cell mRNA sequencing. Our results demonstrate that T cells mapped at single-cell resolution have dramatic transcriptomic changes early after initiation of DAA and many of these changes are sustained after completion of DAA therapy. Specifically, we see a significant reduction in transcripts associated with innate immune activation and interferon signaling such as ISG15, ISG20, IFIT3, OAS and MX1 in many different T cell subsets. Furthermore, we find an early upregulation of a gene involved in suppression of immune activation, DUSP1, in circulating T cells. Conclusion: This study provides the first in-depth transcriptomic analysis at the single-cell level of patients undergoing DAA therapy, demonstrating that IFN-free antiviral therapy in chronic HCV infection induces hitherto unrecognized shifts in innate immune and interferon signaling within T cell populations early, during, and long-term after treatment. The present study provides a rich data source to explore the effects of DAA treatment on bulk T cells.
format	article
author	Matthew A Burchill Matthew P Salomon Lucy Golden-Mason Amanda Wieland Ana C Maretti-Mira Michael Gale Hugo R Rosen
author_facet	Matthew A Burchill Matthew P Salomon Lucy Golden-Mason Amanda Wieland Ana C Maretti-Mira Michael Gale Hugo R Rosen
author_sort	Matthew A Burchill
title	Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes.
title_short	Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes.
title_full	Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes.
title_fullStr	Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes.
title_full_unstemmed	Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes.
title_sort	single-cell transcriptomic analyses of t cells in chronic hcv-infected patients dominated by daa-induced interferon signaling changes.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/4b3c7cb12eb447ffbe8a00b8895b480b
work_keys_str_mv	AT matthewaburchill singlecelltranscriptomicanalysesoftcellsinchronichcvinfectedpatientsdominatedbydaainducedinterferonsignalingchanges AT matthewpsalomon singlecelltranscriptomicanalysesoftcellsinchronichcvinfectedpatientsdominatedbydaainducedinterferonsignalingchanges AT lucygoldenmason singlecelltranscriptomicanalysesoftcellsinchronichcvinfectedpatientsdominatedbydaainducedinterferonsignalingchanges AT amandawieland singlecelltranscriptomicanalysesoftcellsinchronichcvinfectedpatientsdominatedbydaainducedinterferonsignalingchanges AT anacmarettimira singlecelltranscriptomicanalysesoftcellsinchronichcvinfectedpatientsdominatedbydaainducedinterferonsignalingchanges AT michaelgale singlecelltranscriptomicanalysesoftcellsinchronichcvinfectedpatientsdominatedbydaainducedinterferonsignalingchanges AT hugorrosen singlecelltranscriptomicanalysesoftcellsinchronichcvinfectedpatientsdominatedbydaainducedinterferonsignalingchanges
_version_	1718375719863582720

Single-cell transcriptomic analyses of T cells in chronic HCV-infected patients dominated by DAA-induced interferon signaling changes.

Ejemplares similares