ArticleThe Journal of clinical investigation2010
Reconstruction of the complete human cytomegalovirus genome in a BAC reveals RL13 to be a potent inhibitor of replication.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 183 papers.
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Who cites it
183 citing papers in PubMed, 276 citations in OpenAlex.
- A novel hollow-fiber infection model (HFIM) for antiviral PK/PD studies of CMV infection.Antimicrobial agents and chemotherapy · 2026Article
- Article
- Human cytomegalovirus at the maternal-fetal interface: an overview of pathogenesis, defence, and interventions.Clinical science (London, England : 1979) · 2026Review
- Human herpesvirus evasion of humoral immunity and implications for vaccine development.Nature reviews. Microbiology · 2026Review
- A Potent Inhibitor of Human Cytomegalovirus Infection Works Post-Entry Specifically in Differentiating Myelo-Monocytic Cells.Pathogens (Basel, Switzerland) · 2026Article
- Essentiality and dynamic expression of the human tRNA pool during viral infection.Molecular systems biology · 2026Article
- Interstrain recombinants of human cytomegalovirus uncouple glycoprotein display, virion infectivity, and spread characteristics.Journal of virology · 2026Article
- Development of a Chemical Probe to Enable Characterization of the Casein Kinase 1γ Subfamily.Journal of medicinal chemistry · 2026Article
- A viral glycoprotein targets IgGEMBO molecular medicine · 2026Article
- Selective decoupling of IgG1 binding to viral Fc receptors restores antibody-mediated NK cell activation against HCMV.Cell reports · 2025Article
- Repurposing of the bisbenzimide antibiotic Ridinilazole as an antiviral compound against human cytomegalovirus.The Journal of general virology · 2025Article
- Specificity and functional humoral immune responses induced by the VBI-1501A eVLP HCMV gB vaccine compared to the gB/MF59 vaccine.Human vaccines & immunotherapeutics · 2025Article
- The immune response to human cytomegalovirus: impact of age, co-morbidities and the significance of anti-viral activity assessment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- Inhibition of human cytomegalovirus replication by valaciclovir.The Journal of general virology · 2025Article
- Virion proteomics of genetically intact HCMV reveals a regulator of envelope glycoprotein composition that protects against humoral immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Interstrain Recombinants of Human Cytomegalovirus Reveal Complex Genetic Correlates and Epistasis Influencing Glycoprotein Display, Virion Infectivity and Spread Characteristics.bioRxiv : the preprint server for biology · 2025Article
- Development of a chemical probe to enable characterization of the casein kinase 1γ subfamily.bioRxiv : the preprint server for biology · 2025Article
- Replication-deficient whole-virus vaccines against cytomegalovirus induce protective immunity in a guinea pig congenital infection model.Journal of virology · 2025Article
- Small glycomimetic antagonists of the cytomegalovirus glycoprotein UL141 prevent binding to TRAIL death receptor.The Journal of biological chemistry · 2025Article
- Nano-Flow Cytometry-Guided Discrimination and Separation of Human Cytomegalovirus Virions and Extracellular Vesicles.Journal of extracellular vesicles · 2025Article
123 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Human cytomegalovirus (HCMV) in clinical material cannot replicate efficiently in vitro until it has adapted by mutation. Consequently, wild-type HCMV differ fundamentally from the passaged strains used for research. To generate a genetically intact source of HCMV, we cloned strain Merlin into a self-excising BAC. The Merlin BAC clone had mutations in the RL13 gene and UL128 locus that were acquired during limited replication in vitro prior to cloning. The complete wild-type HCMV gene complement was reconstructed by reference to the original clinical sample. Characterization of viruses generated from repaired BACs revealed that RL13 efficiently repressed HCMV replication in multiple cell types; moreover, RL13 mutants rapidly and reproducibly emerged in transfectants. Virus also acquired mutations in genes UL128, UL130, or UL131A, which inhibited virus growth specifically in fibroblast cells in wild-type form. We further report that RL13 encodes a highly glycosylated virion envelope protein and thus has the potential to modulate tropism. To overcome rapid emergence of mutations in genetically intact HCMV, we developed a system in which RL13 and UL131A were conditionally repressed during virus propagation. This technological advance now permits studies to be undertaken with a clonal, characterized HCMV strain containing the complete wild-type gene complement and promises to enhance the clinical relevance of fundamental research on HCMV.
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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.