Human cytomegalovirus induces neuronal gene expression through IE1 for viral maturation

Laurel E. Kelnhofer-Millevolte, Julian R. Smith, Daniel H. Nguyen, Lea S. Wilson, Hannah C. Lewis, Edward A. Arnold, Mia R. Brinkley, Kihye Shin, Jin-Hyun Ahn, Eui Tae Kim, Katarzyna Kulej, Adam P. Geballe, Srinivas Ramachandran and Daphne C. Avgousti ()
Additional contact information
Laurel E. Kelnhofer-Millevolte: Fred Hutchinson Cancer Center
Julian R. Smith: Fred Hutchinson Cancer Center
Daniel H. Nguyen: Fred Hutchinson Cancer Center
Lea S. Wilson: Fred Hutchinson Cancer Center
Hannah C. Lewis: Fred Hutchinson Cancer Center
Edward A. Arnold: Fred Hutchinson Cancer Center
Mia R. Brinkley: Fred Hutchinson Cancer Center
Kihye Shin: Jeju National University College of Medicine
Jin-Hyun Ahn: Sungkyunkwan University School of Medicine
Eui Tae Kim: Jeju National University College of Medicine
Katarzyna Kulej: Memorial Sloan Kettering Cancer Center
Adam P. Geballe: Fred Hutchinson Cancer Center
Srinivas Ramachandran: University of Colorado School of Medicine
Daphne C. Avgousti: Fred Hutchinson Cancer Center

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Viral invasion of the host cell causes some of the most dramatic changes in biology. Human cytomegalovirus (HCMV) extensively remodels host cells, altering nuclear shape and generating a cytoplasmic viral-induced assembly compartment (vIAC). How these striking morphology changes occur in the context of host gene regulation is still emerging. Histone variant macroH2A1 is both important for maintaining nuclear integrity and functions to promote herpes simplex virus infection. Therefore, we hypothesized it may also function in cytomegalovirus infection. Here, we discovered that macroH2A1 is necessary for HCMV-induced cellular reorganization and formation of infectious progeny. Using RNA-seq in infected cells, we find that while all viral genes are highly expressed in the absence of macroH2A1, many HCMV-induced host genes are not. Remarkably, hundreds of these HCMV-induced macroH2A1-dependent host genes are associated with a neuronal signature. Further, we find that HCMV immediate early protein, IE1, is both necessary and sufficient to induce these neuronal genes, providing a mechanism of activation. Together, our findings demonstrate that HCMV hijacks a dormant neuronal secretory pathway through chromatin manipulation for efficient virion maturation.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61915-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61915-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61915-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().