Human cytomegalovirus induces neuronal gene expression through IE1 for viral maturation

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. Here, we discovered that histone variant macroH2A1 is necessary for formation of infectious progeny and HCMV-induced reorganization of the host cell. Using RNA-seq we found that while all viral genes were highly expressed in the absence of macroH2A1, many HCMV-induced host genes were not. Remarkably, hundreds of these HCMV-induced macroH2A1-dependent host genes are associated with neuronal synapse formation and vesicle trafficking. Further, we found that HCMV immediate early protein, IE1, is 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.

INSTRUMENT(S):

ORGANISM(S): Cytomegalovirus Homo Sapiens (human)

TISSUE(S): Cell Culture, Fibroblast

DISEASE(S): Viral Infectious Disease

SUBMITTER: Alex Kentsis  

LAB HEAD: Alex Kentsis, MD, PhD

PROVIDER: PXD061284 | Pride | 2026-02-09

REPOSITORIES: Pride