Journal Article

DZNE-2026-00307

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Cytomegalovirus-encoded immediate early 1 protein perturbs neural progenitor proliferation via interfering with host PML-DISC1 interaction.

Saito, A. ; Tankou, S. ; Ishii, K. ; Sakao-Suzuki, M. ; Oh, E. C. ; Murdoch, H. ; Namkung, H. ; Adelakun, S. ; Furukori, K. ; Fujimuro, M. ; Salomoni, P.DZNE* ; Maul, G. G. ; Hayward, G. S. ; Tang, Q. ; Yolken, R. H. ; Houslay, M. D. ; Katsanis, N. ; Kosugi, I. ; Yang, K. ; Kamiya, A. ; Ishizuka, K. ; Sawa, A.

2026
Soc. Bethesda, Md.

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Please use a persistent id in citations: doi:10.1016/j.jbc.2026.111269

Abstract: Congenital cytomegalovirus (CMV) infection is the most common perinatal infection, affecting up to 0.5% of infants. This elicits long-term disabilities that include neuropsychiatric manifestations, such as intellectual disability, microcephaly. Despite its high prevalence, the underlying mechanism of how congenitally acquired CMV infection causes brain pathology remain unknown. Here, we discovered the molecular interplay of key host (DISC1 and promyelocytic leukemia [PML]) and viral (immediate early 1 [IE1]) proteins within the neural progenitor cells, which underlay an attenuated neural progenitor proliferation in congenital CMV infection. Abolishing the viral IE1 protein by delivering IE1-targeting CRISPR/Cas9 to fetal brain rescued this progenitor cell deficit, a key pathology in congenital CMV infection. A selective targeting to a viral-specific protein by the CRISPR/Cas9 system is minimal in off-target effects. We further observed that CMV-encoded IE1 protein interferes with host PML-DISC1 interaction, resulting in disturbance of the Notch pathway in vitro and in embryonic brains. Therefore, we believe that a pivotal role of IE1 in an attenuated neural progenitor proliferation in the developing cortex through its interfering with interaction between host DISC1 and PML proteins.

Keyword(s): Neural Stem Cells: metabolism (MeSH) ; Neural Stem Cells: pathology (MeSH) ; Neural Stem Cells: virology (MeSH) ; Neural Stem Cells: cytology (MeSH) ; Humans (MeSH) ; Cell Proliferation (MeSH) ; Nerve Tissue Proteins: metabolism (MeSH) ; Nerve Tissue Proteins: genetics (MeSH) ; Promyelocytic Leukemia Protein: metabolism (MeSH) ; Promyelocytic Leukemia Protein: genetics (MeSH) ; Cytomegalovirus: metabolism (MeSH) ; Cytomegalovirus: genetics (MeSH) ; Immediate-Early Proteins: metabolism (MeSH) ; Immediate-Early Proteins: genetics (MeSH) ; Animals (MeSH) ; Cytomegalovirus Infections: metabolism (MeSH) ; Cytomegalovirus Infections: congenital (MeSH) ; Cytomegalovirus Infections: pathology (MeSH) ; Cytomegalovirus Infections: genetics (MeSH) ; Mice (MeSH) ; CRISPR-Cas Systems (MeSH) ; CRISPR/Cas ; DISC1 ; PML ; brain ; congenital infection ; cytomegalovirus ; neural progenitor ; neurodevelopment ; virus ; IE1 protein, cytomegalovirus ; Nerve Tissue Proteins ; Promyelocytic Leukemia Protein ; Immediate-Early Proteins ; DISC1 protein, human ; PML protein, human

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Contributing Institute(s):

1. Nuclear Function in CNS Pathophysiology (AG Salomoni)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2026

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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