Systemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo.

2.50
Hdl Handle:
http://hdl.handle.net/10033/621028
Title:
Systemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo.
Authors:
Hirche, Christoph; Frenz, Theresa; Haas, Simon F; Döring, Marius; Borst, Katharina; Tegtmeyer, Pia-K; Brizic, Ilija; Jordan, Stefan; Keyser, Kirsten; Chhatbar, Chintan; Pronk, Eline; Lin, Shuiping; Messerle, Martin; Jonjic, Stipan; Falk, Christine S; Trumpp, Andreas; Essers, Marieke A G; Kalinke, Ulrich ( 0000-0003-0503-9564 )
Abstract:
Quiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation. After resolution of acute MCMV infection, LT-HSCs returned to phenotypic quiescence. However, non-acute MCMV infection induced a sustained inflammatory milieu within the bone marrow that was associated with long-lasting impairment of LT-HSC function. In conclusion, our results show that systemic virus infections fundamentally affect LT-HSCs and that also non-acute inflammatory stimuli in bone marrow donors can affect the reconstitution potential of bone marrow transplants.
Affiliation:
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynnen Str. 7, 30625 Hannover, Germany.
Citation:
Systemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo. 2017, 19 (11):2345-2356 Cell Rep
Journal:
Cell reports
Issue Date:
13-Jun-2017
URI:
http://hdl.handle.net/10033/621028
DOI:
10.1016/j.celrep.2017.05.063
PubMed ID:
28614719
Type:
Article
Language:
en
ISSN:
2211-1247
Appears in Collections:
publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorHirche, Christophen
dc.contributor.authorFrenz, Theresaen
dc.contributor.authorHaas, Simon Fen
dc.contributor.authorDöring, Mariusen
dc.contributor.authorBorst, Katharinaen
dc.contributor.authorTegtmeyer, Pia-Ken
dc.contributor.authorBrizic, Ilijaen
dc.contributor.authorJordan, Stefanen
dc.contributor.authorKeyser, Kirstenen
dc.contributor.authorChhatbar, Chintanen
dc.contributor.authorPronk, Elineen
dc.contributor.authorLin, Shuipingen
dc.contributor.authorMesserle, Martinen
dc.contributor.authorJonjic, Stipanen
dc.contributor.authorFalk, Christine Sen
dc.contributor.authorTrumpp, Andreasen
dc.contributor.authorEssers, Marieke A Gen
dc.contributor.authorKalinke, Ulrichen
dc.date.accessioned2017-08-01T14:19:12Z-
dc.date.available2017-08-01T14:19:12Z-
dc.date.issued2017-06-13-
dc.identifier.citationSystemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo. 2017, 19 (11):2345-2356 Cell Repen
dc.identifier.issn2211-1247-
dc.identifier.pmid28614719-
dc.identifier.doi10.1016/j.celrep.2017.05.063-
dc.identifier.urihttp://hdl.handle.net/10033/621028-
dc.description.abstractQuiescent long-term hematopoietic stem cells (LT-HSCs) are efficiently activated by type I interferon (IFN-I). However, this effect remains poorly investigated in the context of IFN-I-inducing virus infections. Here we report that both vesicular stomatitis virus (VSV) and murine cytomegalovirus (MCMV) infection induce LT-HSC activation that substantially differs from the effects triggered upon injection of synthetic IFN-I-inducing agents. In both infections, inflammatory responses had to exceed local thresholds within the bone marrow to confer LT-HSC cell cycle entry, and IFN-I receptor triggering was not critical for this activation. After resolution of acute MCMV infection, LT-HSCs returned to phenotypic quiescence. However, non-acute MCMV infection induced a sustained inflammatory milieu within the bone marrow that was associated with long-lasting impairment of LT-HSC function. In conclusion, our results show that systemic virus infections fundamentally affect LT-HSCs and that also non-acute inflammatory stimuli in bone marrow donors can affect the reconstitution potential of bone marrow transplants.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleSystemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo.en
dc.typeArticleen
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynnen Str. 7, 30625 Hannover, Germany.en
dc.identifier.journalCell reportsen

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