Epigenetic reprogramming of host and viral genes by human cytomegalovirus infection in Kasumi-3 myeloid progenitor cells at early times postinfection

Eleonora Forte*, Fatma Ayaloglu Butun, Christian Marinaccio, Matthew John Schipma, Andrea Piunti, Mark W. Schroeder, Manoj Kandpal, Ali Shilatifard, Michael Messod Abecassis, Mary Hummel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Human cytomegalovirus (HCMV) establishes latency in myeloid cells. Using the Kasumi-3 latency model, we previously showed that lytic gene expression is activated prior to the establishment of latency in these cells. The early events in infection may have a critical role in shaping the establishment of latency. Here, we have used an integrative multi-omics approach to investigate dynamic changes in host and HCMV gene expression and epigenomes at early times postinfection. Our results show dynamic changes in viral gene expression and viral chromatin. Analyses of polymerase II (Pol II), histone 3 lysine 27 acetylation (H3K27Ac), and histone 3 lysine 27 trimethylation (H3K27me3) occupancy of the viral genome showed that (i) Pol II occupancy was highest at the major IE promoter (MIEP) at 4 h postinfection. However, it was observed throughout the genome. (ii) At 24 h, H3K27Ac was localized to the major immediate early promoter/enhancer and to a possible second enhancer in the origin of replication oriLyt; (iii) viral chromatin was broadly accessible at 24 hpi. In addition, although HCMV infection activated expression of some host genes, we observed an overall loss of de novo transcription. This was associated with loss of promoter-proximal Pol II and H3K27Ac but not with changes in chromatin accessibility or a switch in modification of H3K27. IMPORTANCE Human cytomegalovirus (HCMV) is an important human pathogen in immunocompromised hosts and developing fetuses. Current antiviral therapies are limited by toxicity and emergence of resistant strains. Our studies highlight emerging concepts that challenge current paradigms of regulation of HCMV gene expression in myeloid cells. In addition, our studies show that HCMV has a profound effect on de novo transcription and the cellular epigenome. These results may have implications for mechanisms of viral pathogenesis.

Original languageEnglish (US)
Article numbere00183
JournalJournal of virology
Volume95
Issue number11
DOIs
StatePublished - Jun 2021

Keywords

  • Epigenetics
  • Gene expression
  • Herpesviruses
  • Human cytomegalovirus

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Fingerprint

Dive into the research topics of 'Epigenetic reprogramming of host and viral genes by human cytomegalovirus infection in Kasumi-3 myeloid progenitor cells at early times postinfection'. Together they form a unique fingerprint.

Cite this