Year: 2025
Type: article
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. HCMV rearranges the host cell to produce infectious virus but molecular details are still unclear. Here, the authors analyze the transcriptome of infected cells and show that HCMV turns on dormant neuronal genes through chromatin manipulation to achieve this goal.
Source: Nature Communications
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, Fred Hutchinson Cancer Research Center, University of Miami, University of Washington, National Research Foundation, National Research Foundation of Korea, Ministry of Science and ICT, South Korea, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, University of Colorado School of Medicine, Anschutz Medical Campus
Awards: G1305388156, G1387272876, Evolution and mechanisms of cytomegalovirus antagonism of host cell defenses, G1713994812, G2076406414, G2913107559, G3148284750, G3196308001, G3679387945, Diseases of Public Health Importance Training Grant, G4712995822, G5558775386, Investigating chromatin mechanisms using viral systems, Maintenance of cellular memory through replication, G746389200, G9000085113, G9000145880, G9000186211, G9000277173, Cancer Center Support Grant, Cancer Center Support Grant, G973051238
OpenAlex ID: W4413055213