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Systemic Virus Infections Differentially Modulate Cell Cycle State and Functionality of Long-Term Hematopoietic Stem Cells In Vivo.
Hirche, Christoph Frenz, Theresa Haas, Simon F Döring, Marius Borst, Katharina Tegtmeyer, Pia-K Brizic, Ilija Jordan, Stefan Keyser, Kirsten Chhatbar, Chintan
Hirche, Christoph
Frenz, Theresa
Haas, Simon F
Döring, Marius
Borst, Katharina
Tegtmeyer, Pia-K
Brizic, Ilija
Jordan, Stefan
Keyser, Kirsten
Chhatbar, Chintan
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2017-06-13
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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.
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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
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en
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2211-1247