ArticleJournal of virology2008
Transactivation of cellular genes involved in nucleotide metabolism by the regulatory IE1 protein of murine cytomegalovirus is not critical for viral replicative fitness in quiescent cells and host tissues.
Article in Journal of virology, 2008. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Human Cytomegalovirus IE1 Impairs Neuronal Migration by Downregulating Connexin 43.Journal of virology · 2023Article
- Direct antigen presentation is the canonical pathway of cytomegalovirus CD8 T-cell priming regulated by balanced immune evasion ensuring a strong antiviral response.Frontiers in immunology · 2023Article
- A congenital CMV infection model for follow-up studies of neurodevelopmental disorders, neuroimaging abnormalities, and treatment.JCI insight · 2022Article
- Emerging Mechanisms of GmBio · 2021Review
- Enteric Ganglioneuritis, a Common Feature in a Subcutaneous TBEV Murine Infection Model.Microorganisms · 2021Article
- The herpesviral antagonist m152 reveals differential activation of STING-dependent IRF and NF-κB signaling and STING's dual role during MCMV infection.The EMBO journal · 2019Article
- Bile Acids Act as Soluble Host Restriction Factors Limiting Cytomegalovirus Replication in Hepatocytes.Journal of virology · 2016Article
- Principles for studying in vivo attenuation of virus mutants: defining the role of the cytomegalovirus gH/gL/gO complex as a paradigm.Medical microbiology and immunology · 2015Review
- Cytomegalovirus immune evasion of myeloid lineage cells.Medical microbiology and immunology · 2015Review
- Mechanism of tumor remission by cytomegalovirus in a murine lymphoma model: evidence for involvement of virally induced cellular interleukin-15.Medical microbiology and immunology · 2015Article
- An endocytic YXXΦ (YRRF) cargo sorting motif in the cytoplasmic tail of murine cytomegalovirus AP2 'adapter adapter' protein m04/gp34 antagonizes virus evasion of natural killer cells.Medical microbiology and immunology · 2015Article
- A new reporter mouse cytomegalovirus reveals maintained immediate-early gene expression but poor virus replication in cycling liver sinusoidal endothelial cells.Virology journal · 2013Article
- Viral latency drives 'memory inflation': a unifying hypothesis linking two hallmarks of cytomegalovirus infection.Medical microbiology and immunology · 2012Review
- Ablation of the regulatory IE1 protein of murine cytomegalovirus alters in vivo pro-inflammatory TNF-alpha production during acute infection.PLoS pathogens · 2012Article
- H2B homology region of major immediate-early protein 1 is essential for murine cytomegalovirus to disrupt nuclear domain 10, but is not important for viral replication in cell culture.The Journal of general virology · 2011Article
- Reverse genetics modification of cytomegalovirus antigenicity and immunogenicity by CD8 T-cell epitope deletion and insertion.Journal of biomedicine & biotechnology · 2011Review
- Enhancerless cytomegalovirus is capable of establishing a low-level maintenance infection in severely immunodeficient host tissues but fails in exponential growth.Journal of virology · 2010Article
- Deletion of the rat cytomegalovirus immediate-early 1 gene results in a virus capable of establishing latency, but with lower levels of acute virus replication and latency that compromise reactivation efficiency.The Journal of general virology · 2010Article
- Immune evasion proteins of murine cytomegalovirus preferentially affect cell surface display of recently generated peptide presentation complexes.Journal of virology · 2010Article
- Liver sinusoidal endothelial cells are a site of murine cytomegalovirus latency and reactivation.Journal of virology · 2009Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite its high coding capacity, murine CMV (mCMV) does not encode functional enzymes for nucleotide biosynthesis. It thus depends on cellular enzymes, such as ribonucleotide reductase (RNR) and thymidylate synthase (TS), to be supplied with deoxynucleoside triphosphates (dNTPs) for its DNA replication. Viral transactivation of these cellular genes in quiescent cells of host tissues is therefore a parameter of viral fitness relevant to pathogenicity. Previous work has shown that the IE1, but not the IE3, protein of mCMV transactivates RNR and TS gene promoters and has revealed an in vivo attenuation of the mutant virus mCMV-DeltaIE1. It was attractive to propose the hypothesis that lack of transactivation by IE1 and a resulting deficiency in the supply of dNTPs are the reasons for growth attenuation. Here, we have tested this hypothesis with the mutant virus mCMV-IE1-Y165C expressing an IE1 protein that selectively fails to transactivate RNR and TS in quiescent cells upon transfection while maintaining the capacity to disperse repressive nuclear domains (ND10). Our results confirm in vivo attenuation of mCMV-DeltaIE1, as indicated by a longer doubling time in host organs, whereas mCMV-IE1-Y165C replicated like mCMV-WT and the revertant virus mCMV-IE1-C165Y. Notably, the mutant virus transactivated RNR and TS upon infection of quiescent cells, thus indicating that IE1 is not the only viral transactivator involved. We conclude that transactivation of cellular genes of dNTP biosynthesis is ensured by redundancy and that attenuation of mCMV-DeltaIE1 results from the loss of other critical functions of IE1, with its function in the dispersal of ND10 being a promising candidate.
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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.