Journal
CELL HOST & MICROBE
Volume 27, Issue 1, Pages 104-+Publisher
CELL PRESS
DOI: 10.1016/j.chom.2019.11.013
Keywords
-
Categories
Funding
- National Institutes of Health, United States NIAID [P01 A127335, R01 A121640]
Ask authors/readers for more resources
Infection with human cytomegalovirus (HCMV) remains a significant cause of morbidity and mortality following hematopoietic stem cell transplant (HSCT) because of various hematologic problems, including myelosuppression. Here, we demonstrate that latently expressed HCMV miR-US5-2 downregulates the transcriptional repressor NGFI-A binding protein (NAB1) to induce myelosuppression of uninfected CD34(+) hematopoietic progenitor cells (HPCs) through an increase in TGF-beta production. Infection of HPCs with an HCMV Delta miR-US5-2 mutant resulted in decreased TGF-beta expression and restoration of myelopoiesis. In contrast, we show that infected HPCs are refractory to TGF-beta signaling as another HCMV miRNA, miR-UL22A, downregulates SMAD3, which is required for maintenance of latency. Our data suggest that latently expressed viral miRNAs manipulate stem cell homeostasis by inducing secretion of TGF-beta while protecting infected HPCs from TGF-beta-mediated effects on viral latency and reactivation. These observations provide a mechanism through which HCMV induces global myelosuppression following HSCT while maintaining lifelong infection in myeloid lineage cells.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available