ArticlePloS one2012
The human cytomegalovirus DNA polymerase processivity factor UL44 is modified by SUMO in a DNA-dependent manner.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Letermovir shows antiviral and neuroprotective effects in differentiating neurons and cerebral organoids mimicking human developing brain.Cellular and molecular life sciences : CMLS · 2026Article
- A Highly Sensitive BRET-Based Reporter for Live-Cell Detection of HIV-1 Protease Activity and Inhibitor Screening.Viruses · 2025Article
- Article
- Complex roles for proliferating cell nuclear antigen in restricting human cytomegalovirus replication.bioRxiv : the preprint server for biology · 2025Article
- New dengue virus inhibitors targeting NS3-NS5 interaction identified byFrontiers in microbiology · 2025Article
- A UL26-PIAS1 complex antagonizes anti-viral gene expression during Human Cytomegalovirus infection.PLoS pathogens · 2024Article
- Review
- Article
- SUMOylation and Viral Infections of the Brain.Pathogens (Basel, Switzerland) · 2022Review
- SUMOylation in Viral Replication and Antiviral Defense.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Article
- Viruses, SUMO, and immunity: the interplay between viruses and the host SUMOylation system.Journal of neurovirology · 2021Review
- SUMO: a novel target for anti-coronavirus therapy.Pathogens and global health · 2021Review
- Article
- Sumoylation of the Carboxy-Terminal of Human Cytomegalovirus DNA Polymerase Processivity Factor UL44 Attenuates Viral DNA Replication.Frontiers in microbiology · 2021Article
- Human Cytomegalovirus Primary Infection and Reactivation: Insights From Virion-Carried Molecules.Frontiers in microbiology · 2020Review
- Orchestration of protein acetylation as a toggle for cellular defense and virus replication.Nature communications · 2018Article
- An improved method for identifying SUMOylation sites of viral proteins.Virologica Sinica · 2017Article
- Viral Interplay with the Host Sumoylation System.Advances in experimental medicine and biology · 2017Review
- SUMO Modification Stabilizes Enterovirus 71 Polymerase 3D To Facilitate Viral Replication.Journal of virology · 2016Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the replication of human cytomegalovirus (HCMV) genome, the viral DNA polymerase subunit UL44 plays a key role, as by binding both DNA and the polymerase catalytic subunit it confers processivity to the holoenzyme. However, several lines of evidence suggest that UL44 might have additional roles during virus life cycle. To shed light on this, we searched for cellular partners of UL44 by yeast two-hybrid screenings. Intriguingly, we discovered the interaction of UL44 with Ubc9, an enzyme involved in the covalent conjugation of SUMO (Small Ubiquitin-related MOdifier) to cellular and viral proteins. We found that UL44 can be extensively sumoylated not only in a cell-free system and in transfected cells, but also in HCMV-infected cells, in which about 50% of the protein resulted to be modified at late times post-infection, when viral genome replication is accomplished. Mass spectrometry studies revealed that UL44 possesses multiple SUMO target sites, located throughout the protein. Remarkably, we observed that binding of UL44 to DNA greatly stimulates its sumoylation both in vitro and in vivo. In addition, we showed that overexpression of SUMO alters the intranuclear distribution of UL44 in HCMV-infected cells, and enhances both virus production and DNA replication, arguing for an important role for sumoylation in HCMV life cycle and UL44 function(s). These data report for the first time the sumoylation of a viral processivity factor and show that there is a functional interplay between the HCMV UL44 protein and the cellular sumoylation system.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.