HCMV miR-US22 down-regulation of EGR-1 regulates CD34+ hematopoietic progenitor cell proliferation and viral reactivation

Iliyana Mikell, Lindsey B. Crawford, Meaghan H. Hancock, Jennifer Mitchell, Jason Buehler, Felicia Goodrum, Jay A. Nelson

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Reactivation of latent Human Cytomegalovirus (HCMV) in CD34+ hematopoietic progenitor cells (HPCs) is closely linked to hematopoiesis. Viral latency requires maintenance of the progenitor cell quiescence, while reactivation initiates following mobilization of HPCs to the periphery and differentiation into CD14+ macrophages. Early growth response gene 1 (EGR-1) is a transcription factor activated by Epidermal growth factor receptor (EGFR) signaling that is essential for the maintenance of CD34+ HPC self-renewal in the bone marrow niche. Down-regulation of EGR-1 results in mobilization and differentiation of CD34+ HPC from the bone marrow to the periphery. In the current study we demonstrate that the transcription factor EGR-1 is directly targeted for down-regulation by HCMV miR-US22 that results in decreased proliferation of CD34+ HPCs and a decrease in total hematopoietic colony formation. We also show that an HCMV miR-US22 mutant fails to reactivate in CD34+ HPCs, indicating that expression of EGR-1 inhibits viral reactivation. Since EGR-1 promotes CD34+ HPC self-renewal in the bone marrow niche, HCMV miR-US22 down-regulation of EGR-1 is a necessary step to block HPC self-renewal and proliferation to induce a cellular differentiation pathway necessary to promote reactivation of virus.

Original languageEnglish (US)
Pages (from-to)e1007854
JournalPLoS pathogens
Volume15
Issue number11
DOIs
StatePublished - Nov 1 2019

Fingerprint

Hematopoietic Stem Cells
Cytomegalovirus
Down-Regulation
Cell Proliferation
Growth
Genes
Bone Marrow
Early Growth Response Protein 1
Maintenance
Virus Latency
Hematopoiesis
Epidermal Growth Factor Receptor
Transcription Factors
Stem Cells
Macrophages
Viruses
Cell Self Renewal

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

HCMV miR-US22 down-regulation of EGR-1 regulates CD34+ hematopoietic progenitor cell proliferation and viral reactivation. / Mikell, Iliyana; Crawford, Lindsey B.; Hancock, Meaghan H.; Mitchell, Jennifer; Buehler, Jason; Goodrum, Felicia; Nelson, Jay A.

In: PLoS pathogens, Vol. 15, No. 11, 01.11.2019, p. e1007854.

Research output: Contribution to journalArticle

Mikell, Iliyana ; Crawford, Lindsey B. ; Hancock, Meaghan H. ; Mitchell, Jennifer ; Buehler, Jason ; Goodrum, Felicia ; Nelson, Jay A. / HCMV miR-US22 down-regulation of EGR-1 regulates CD34+ hematopoietic progenitor cell proliferation and viral reactivation. In: PLoS pathogens. 2019 ; Vol. 15, No. 11. pp. e1007854.
@article{8a759cb9ecb94f5e9fdfb471f0060d0e,
title = "HCMV miR-US22 down-regulation of EGR-1 regulates CD34+ hematopoietic progenitor cell proliferation and viral reactivation",
abstract = "Reactivation of latent Human Cytomegalovirus (HCMV) in CD34+ hematopoietic progenitor cells (HPCs) is closely linked to hematopoiesis. Viral latency requires maintenance of the progenitor cell quiescence, while reactivation initiates following mobilization of HPCs to the periphery and differentiation into CD14+ macrophages. Early growth response gene 1 (EGR-1) is a transcription factor activated by Epidermal growth factor receptor (EGFR) signaling that is essential for the maintenance of CD34+ HPC self-renewal in the bone marrow niche. Down-regulation of EGR-1 results in mobilization and differentiation of CD34+ HPC from the bone marrow to the periphery. In the current study we demonstrate that the transcription factor EGR-1 is directly targeted for down-regulation by HCMV miR-US22 that results in decreased proliferation of CD34+ HPCs and a decrease in total hematopoietic colony formation. We also show that an HCMV miR-US22 mutant fails to reactivate in CD34+ HPCs, indicating that expression of EGR-1 inhibits viral reactivation. Since EGR-1 promotes CD34+ HPC self-renewal in the bone marrow niche, HCMV miR-US22 down-regulation of EGR-1 is a necessary step to block HPC self-renewal and proliferation to induce a cellular differentiation pathway necessary to promote reactivation of virus.",
author = "Iliyana Mikell and Crawford, {Lindsey B.} and Hancock, {Meaghan H.} and Jennifer Mitchell and Jason Buehler and Felicia Goodrum and Nelson, {Jay A.}",
year = "2019",
month = "11",
day = "1",
doi = "10.1371/journal.ppat.1007854",
language = "English (US)",
volume = "15",
pages = "e1007854",
journal = "PLoS Pathogens",
issn = "1553-7366",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - HCMV miR-US22 down-regulation of EGR-1 regulates CD34+ hematopoietic progenitor cell proliferation and viral reactivation

AU - Mikell, Iliyana

AU - Crawford, Lindsey B.

AU - Hancock, Meaghan H.

AU - Mitchell, Jennifer

AU - Buehler, Jason

AU - Goodrum, Felicia

AU - Nelson, Jay A.

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Reactivation of latent Human Cytomegalovirus (HCMV) in CD34+ hematopoietic progenitor cells (HPCs) is closely linked to hematopoiesis. Viral latency requires maintenance of the progenitor cell quiescence, while reactivation initiates following mobilization of HPCs to the periphery and differentiation into CD14+ macrophages. Early growth response gene 1 (EGR-1) is a transcription factor activated by Epidermal growth factor receptor (EGFR) signaling that is essential for the maintenance of CD34+ HPC self-renewal in the bone marrow niche. Down-regulation of EGR-1 results in mobilization and differentiation of CD34+ HPC from the bone marrow to the periphery. In the current study we demonstrate that the transcription factor EGR-1 is directly targeted for down-regulation by HCMV miR-US22 that results in decreased proliferation of CD34+ HPCs and a decrease in total hematopoietic colony formation. We also show that an HCMV miR-US22 mutant fails to reactivate in CD34+ HPCs, indicating that expression of EGR-1 inhibits viral reactivation. Since EGR-1 promotes CD34+ HPC self-renewal in the bone marrow niche, HCMV miR-US22 down-regulation of EGR-1 is a necessary step to block HPC self-renewal and proliferation to induce a cellular differentiation pathway necessary to promote reactivation of virus.

AB - Reactivation of latent Human Cytomegalovirus (HCMV) in CD34+ hematopoietic progenitor cells (HPCs) is closely linked to hematopoiesis. Viral latency requires maintenance of the progenitor cell quiescence, while reactivation initiates following mobilization of HPCs to the periphery and differentiation into CD14+ macrophages. Early growth response gene 1 (EGR-1) is a transcription factor activated by Epidermal growth factor receptor (EGFR) signaling that is essential for the maintenance of CD34+ HPC self-renewal in the bone marrow niche. Down-regulation of EGR-1 results in mobilization and differentiation of CD34+ HPC from the bone marrow to the periphery. In the current study we demonstrate that the transcription factor EGR-1 is directly targeted for down-regulation by HCMV miR-US22 that results in decreased proliferation of CD34+ HPCs and a decrease in total hematopoietic colony formation. We also show that an HCMV miR-US22 mutant fails to reactivate in CD34+ HPCs, indicating that expression of EGR-1 inhibits viral reactivation. Since EGR-1 promotes CD34+ HPC self-renewal in the bone marrow niche, HCMV miR-US22 down-regulation of EGR-1 is a necessary step to block HPC self-renewal and proliferation to induce a cellular differentiation pathway necessary to promote reactivation of virus.

UR - http://www.scopus.com/inward/record.url?scp=85075060646&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85075060646&partnerID=8YFLogxK

U2 - 10.1371/journal.ppat.1007854

DO - 10.1371/journal.ppat.1007854

M3 - Article

C2 - 31725809

AN - SCOPUS:85075060646

VL - 15

SP - e1007854

JO - PLoS Pathogens

JF - PLoS Pathogens

SN - 1553-7366

IS - 11

ER -