@article{a1c5b2cbe0fe428cabe77391afba452d,
title = "Human Cytomegalovirus miR-US5-2 Downregulation of GAB1 Regulates Cellular Proliferation and UL138 Expression through Modulation of Epidermal Growth Factor Receptor Signaling Pathways",
abstract = "Regulation of epidermal growth factor (EGF) receptor (EGFR) signaling is critical for the replication of human cytomegalovirus (HCMV) as well as latency and reactivation in CD34+ hematopoietic progenitor cells. HCMV microRNAs (miRNAs) provide a means to modulate the signaling activated by EGF through targeting com-ponents of the EGFR signaling pathways. Here, we demonstrate that HCMV miR- US5-2 directly downregulates the critical EGFR adaptor protein GAB1 that mediates activation and sustained signaling through the phosphatidylinositol 3-kinase (PI3K) and MEK/extracellular signal-regulated kinase (ERK) pathways and cellular prolifera¬tion in response to EGF. Expression of HCMV UL138 is regulated by the transcription factor early growth response gene 1 (EGR1) downstream of EGFR-induced MEK/ERK signaling. We show that by targeting GAB1 and attenuating MEK/ERK signaling, miR- US5-2 indirectly regulates EGR1 and UL138 expression, which implicates the miRNA in critical regulation of HCMV latency.",
keywords = "GAB1, UL138, cytomegalovirus, miRNA",
author = "\{Meaghan H\}, \{Hancock H.\} and Jennifer Mitchell and \{Felicia D\}, \{Goodrum D.\} and \{Jay A\}, \{Nelson A.\}",
note = "Funding Information: This work was supported by National Institutes of Health grant R37 AI21640 funded to J.A.N., National Institutes of Health grant R01 AI079059 funded to F.D.G., and National Institutes of Health grant P01 AI127335 funded to J.A.N. and F.D.G. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Rebecca Skalsky, Yan Chen, and Devin Fachko for technical assistance and critical reading of the manuscript as well as Andrew Townsend for assistance with image preparation. Funding Information: Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award number R33AI127607. The content is solely our responsibility and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: Copyright {\textcopyright} 2020 Hancocket al. This is an open-access article distributed under the terms ofthe Creative Commons Attribution 4.0 International license.",
year = "2020",
month = jun,
day = "24",
doi = "10.1128/msphere.00374-20",
language = "English (US)",
volume = "5",
journal = "mSphere",
issn = "2379-5042",
publisher = "American Society for Microbiology",
number = "3",
}