Viral and host network analysis of the human cytomegalovirus transcriptome in latency

• 成果类型: Article
• 署名作者: Collins-McMillen, Donna; Pessoa, Diogo De Oliveira; Zarrella, Kristen; Parkins, Christopher J.; Daily, Michael; McKinzey, David R.; Moorman, Nathaniel J.; Kamil, Jeremy P.; Caposio, Patrizia; Padi, Megha; Goodrum, Felicia D.
• 署名单位: University of Arizona; University of Arizona; University of Arizona; Arizona Center Cancer Care; Oregon Health & Science University; University of North Carolina; University of North Carolina Chapel Hill; University of North Carolina School of Medicine; Louisiana State University System; Louisiana State University Health Sciences Center at Shreveport; University of Arizona; University of Arizona
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13128
• DOI: 10.1073/pnas.2416114122
• 发表日期: 2025-05-28
• 关键词: ppar-gamma; gene-expression; differentiation; virus

摘要

The human cytomegalovirus (HCMV) UL135 and UL138 genes play opposing roles regulating latency and reactivation in CD34+ human progenitor cells. We designed an RNA sequencing study to compare the transcriptional profile of HCMV infection in the presence and absence of these genes using the Tohoku Hospital Pediatrics-1 (THP-1) monocytic cell line model for latency. Relative to primary cell models, THP-1 cells offer the strength of a homogenous population that uniformly silences gene expression and will synchronously reexpress viral genes following stimulation to differentiate, which models early phases of viral reactivation. The loss of UL138 resulted in elevated levels of viral gene expression and in spontaneous adhesion of distinct cell populations that support HCMV gene expression and genome synthesis. The loss of UL135 resulted in diminished viral gene expression during an initial burst that occurs as latency is established and in no expression of eleven viral genes from the ULb ' region even following differentiation and reexpression of viral genes. Transcriptional network analysis revealed host transcription factors (TFs) with potential to regulate the ULb ' genes in coordination with pUL135. We show that the cellular TF peroxisome proliferator-activated receptor gamma binds to the viral genome and influences the expression of UL133-UL138 locus genes. Our results define roles for UL135 and UL138 in regulation of patterns of viral gene expression for the establishment of latency and reexpression of viral genes for reactivation and reveal insights into differentiation-linked mechanisms of transcriptional control of the HCMV genome.