ArticleJournal of virology2012
A mutation deleting sequences encoding the amino terminus of human cytomegalovirus UL84 impairs interaction with UL44 and capsid localization.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 24 citations in OpenAlex.
- Cis and trans acting factors involved in human cytomegalovirus experimental and natural latent infection of CD14 (+) monocytes and CD34 (+) cells.PLoS pathogens · 2013Trial
- Comparative evaluation of screening approaches for antiviral monoclonal antibody combinations.Journal of virology · 2026Article
- Isolation and characterization of broadly-neutralizing anti-HCMV-gB antibodies from human donors using a prefusion-stabilized HCMV gB variant.PLoS pathogens · 2026Article
- HCMV encoded UL84 hijacks FHL2 to suppress type I interferon production and enhance viral replication.PLoS pathogens · 2026Article
- Repurposing of the bisbenzimide antibiotic Ridinilazole as an antiviral compound against human cytomegalovirus.The Journal of general virology · 2025Article
- The functions of herpesvirus shuttling proteins in the virus lifecycle.Frontiers in microbiology · 2025Review
- Inhibition of human cytomegalovirus replication by interferon alpha can involve multiple anti-viral factors.The Journal of general virology · 2023Article
- The human cytomegalovirus decathlon: Ten critical replication events provide opportunities for restriction.Frontiers in cell and developmental biology · 2022Review
- Identification and characterization of bisbenzimide compounds that inhibit human cytomegalovirus replication.The Journal of general virology · 2021Article
- Characteristics of Immediate-Early 2 (IE2) and UL84 Proteins in UL84-Independent Strains of Human Cytomegalovirus (HCMV).Microbiology spectrum · 2021Article
- The N Terminus of Autographa californica Multiple Nucleopolyhedrovirus DNA Polymerase Is Required for Efficient Viral DNA Replication and Virus and Occlusion Body Production.Journal of virology · 2018Article
- A Role for Myosin Va in Human Cytomegalovirus Nuclear Egress.Journal of virology · 2018Article
- Mechanism of Protein Kinase R Inhibition by Human Cytomegalovirus pTRS1.Journal of virology · 2017Article
- High-Throughput Small Interfering RNA Screening Identifies Phosphatidylinositol 3-Kinase Class II Alpha as Important for Production of Human Cytomegalovirus Virions.Journal of virology · 2016Article
- Human Cytomegalovirus pTRS1 and pIRS1 Antagonize Protein Kinase R To Facilitate Virus Replication.Journal of virology · 2016Article
- Genetic Stability of Bacterial Artificial Chromosome-Derived Human Cytomegalovirus during Culture In Vitro.Journal of virology · 2016Article
- Structure of a herpesvirus nuclear egress complex subunit reveals an interaction groove that is essential for viral replication.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Review
- Dynamic and nucleolin-dependent localization of human cytomegalovirus UL84 to the periphery of viral replication compartments and nucleoli.Journal of virology · 2014Article
- Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Protein-protein interactions are required for many biological functions. Previous work has demonstrated an interaction between the human cytomegalovirus DNA polymerase subunit UL44 and the viral replication factor UL84. In this study, glutathione S-transferase pulldown assays indicated that residues 1 to 68 of UL84 are both necessary and sufficient for efficient interaction of UL84 with UL44 in vitro. We created a mutant virus in which sequences encoding these residues were deleted. This mutant displayed decreased virus replication compared to wild-type virus. Immunoprecipitation assays showed that the mutation decreased but did not abrogate association of UL84 with UL44 in infected cell lysate, suggesting that the association in the infected cell can involve other protein-protein interactions. Further immunoprecipitation assays indicated that IRS1, TRS1, and nucleolin are candidates for such interactions in infected cells. Quantitative real-time PCR analysis of viral DNA indicated that the absence of the UL84 amino terminus does not notably affect viral DNA synthesis. Western blotting experiments and pulse labeling of infected cells with [(35)S]methionine demonstrated a rather modest downregulation of levels of multiple proteins and particularly decreased levels of the minor capsid protein UL85. Electron microscopy demonstrated that viral capsids assemble but are mislocalized in nuclei of cells infected with the mutant virus, with fewer cytoplasmic capsids detected. In sum, deletion of the sequences encoding the amino terminus of UL84 affects interaction with UL44 and virus replication unexpectedly, not viral DNA synthesis. Mislocalization of viral capsids in infected cell nuclei likely contributes to the observed decrease in virus replication.
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