{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE325nnn/GSE325506/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Other"],"species":["Homo sapiens"],"gds_type":["Other"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE325506"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"HSV-1 temporally orchestrates RAP80 ubiquitination to balance viral replication and evasion [Hi-C]","description":"The mechanisms governing the complete replication cycle of herpes simplex virus type 1 (HSV-1) remain incompletely elucidated. Here, we showed that HSV-1 employs a biphasic strategy to dynamically regulate the host protein RAP80 through stage-specific ubiquitination, thereby coordinating its replication cycle. Upon entry, RAP80 undergoes phase separation to form antiviral condensates that encapsulate the viral genome and suppress viral transcription. The HSV-1-encoded E3 ubiquitin ligase ICP0 counteracts this antiviral mechanism by mediating RAP80 ubiquitination to dissolve these condensates, facilitating viral replication. In middle stage, RAP80 depletion leads to accumulation of R-loops and activation of the cGAS–STING–apoptosis axis, threatening viral persistence. In response, in middle and late stage, the viral deubiquitinase UL36USP deubiquitinates and stabilizes RAP80 to suppress R-loop accumulation and this immune-triggered apoptosis. This biphasic regulation of a single host factor represents a sophisticated viral strategy to ensure productive replication and dissemination. Notably, pharmacological disruption of RAP80 ubiquitination using engineered inhibitory peptides potently inhibits HSV-1 replication in vitro and in vivo. Furthermore, RAP80 inhibition enhances both chemosensitivity and oncolytic virotherapy in tumors. These findings reveal a ubiquitination-mediated host–pathogen equilibrium with therapeutic potential in antiviral and anticancer contexts.","dates":{"publication":"2026/03/20"},"accession":"GSE325506","cross_references":{"GSM":["GSM9605332","GSM9605310","GSM9605331","GSM9605330","GSM9605319","GSM9605318","GSM9605339","GSM9605317","GSM9605338","GSM9605316","GSM9605315","GSM9605337","GSM9605336","GSM9605314","GSM9605335","GSM9605313","GSM9605312","GSM9605334","GSM9605333","GSM9605311","GSM9605321","GSM9605320","GSM9605309","GSM9605308","GSM9605329","GSM9605307","GSM9605306","GSM9605328","GSM9605327","GSM9605305","GSM9605304","GSM9605326","GSM9605325","GSM9605324","GSM9605323","GSM9605322"],"GPL":["34284"],"GSE":["325506"],"taxon":["Homo sapiens"]}}