Systemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo.
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Authors
Hirche, ChristophFrenz, 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
Issue Date
2017-06-13
Metadata
Show full item recordAbstract
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.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 RepAffiliation
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH, Feodor-Lynnen Str. 7, 30625 Hannover, Germany.Journal
Cell reportsPubMed ID
28614719Type
ArticleLanguage
enISSN
2211-1247ae974a485f413a2113503eed53cd6c53
10.1016/j.celrep.2017.05.063
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
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