Human Cytomegalovirus UL7, miR-US5-1, and miR-UL112-3p Inactivation of FOXO3a Protects CD34⁺ Hematopoietic Progenitor Cells from Apoptosis.

ABSTRACT: Human cytomegalovirus (HCMV) infection of myeloid lineage cells, such as CD34⁺ hematopoietic progenitor cells (HPCs) or monocytes, results in the upregulation of antiapoptotic cellular proteins that protect the newly infected cells from programmed cell death. The mechanisms used by HCMV to regulate proapoptotic cellular proteins upon infection of CD34⁺ HPCs have not been fully explored. Here, we show that HCMV utilizes pUL7, a secreted protein that signals through the FLT3 receptor, and miR-US5-1 and miR-UL112-3p to reduce the abundance and activity of the proapoptotic transcription factor FOXO3a at early times after infection of CD34⁺ HPCs. Regulation of FOXO3a by pUL7, miR-US5-1, and miR-UL112 results in reduced expression of the proapoptotic BCL2L11</

SUBMITTER: Hancock MH 

PROVIDER: S-EPMC7845589 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature