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| Item Type: | Article |
|---|---|
| Title: | Systemic virus infections differentially modulate cell cycle state and functionality of long-term hematopoietic stem cells in vivo |
| Creators Name: | Hirche, C., Frenz, T., Haas, S.F., Döring, M., Borst, K., Tegtmeyer, P.K., Brizic, I., Jordan, S., Keyser, K., Chhatbar, C., Pronk, E., Lin, S., Messerle, M., Jonjic, S., Falk, C.S., Trumpp, A., Essers, M.A.G. and Kalinke, U. |
| 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. |
| Keywords: | Hematopoietic Stem Cells, Quiescence, Cell Cycle, Stem Cell Activation, Systemic Inflammation, Inflammatory Cytokines, Virus Infections, Stem Cell Function, Bone Marrow Transplantation, Transplant Complications, Animals, Mice |
| Source: | Cell Reports |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press / Elsevier |
| Volume: | 19 |
| Number: | 11 |
| Page Range: | 2345-2356 |
| Date: | 13 June 2017 |
| Official Publication: | https://doi.org/10.1016/j.celrep.2017.05.063 |
| PubMed: | View item in PubMed |
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