Repression of HMGA2 Gene Expression by Human Cytomegalovirus Involves the IE2 86-Kilodalton Protein and Is Necessary for Efficient Viral Replication and Inhibition of Cyclin A Transcription
| العنوان: | Repression of HMGA2 Gene Expression by Human Cytomegalovirus Involves the IE2 86-Kilodalton Protein and Is Necessary for Efficient Viral Replication and Inhibition of Cyclin A Transcription |
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| المؤلفون: | Deborah H. Spector, Charles L. Clark, Rebecca L. Sanders, Mark Shlapobersky |
| المصدر: | Journal of Virology. 80:9951-9961 |
| بيانات النشر: | American Society for Microbiology, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Transcription, Genetic, viruses, Cyclin D, Immunology, Cyclin A, Cytomegalovirus, Biology, Virus Replication, Microbiology, Immediate-Early Proteins, Viral Proteins, Multiplicity of infection, Cyclin D1, Virology, Gene expression, Humans, Gene, Cells, Cultured, Recombination, Genetic, Regulation of gene expression, HMGA2 Protein, Molecular biology, Recombinant Proteins, Virus-Cell Interactions, Gene Expression Regulation, Insect Science, Trans-Activators, biology.protein, RNA, Cyclin A2 |
| الوصف: | Human cytomegalovirus (HCMV) infection results in dysregulation of several cell cycle genes, including inhibition of cyclin A transcription. In this work, we examine the effect of the HCMV infection on expression of the high-mobility group A2 (HMGA2) gene, which encodes an architectural transcription factor that is involved in cyclin A promoter activation. We find that expression of HMGA2 RNA is repressed in infected cells. To determine whether repression of HMGA2 is directly related to the inhibition of cyclin A expression and impacts on the progression of the infection, we constructed an HCMV recombinant that expressed HMGA2. In cells infected with the recombinant virus, cyclin A mRNA and protein are induced, and there is a significant delay in viral early gene expression and DNA replication. To determine the mechanism of HMGA2 repression, we used recombinant viruses that expressed either no IE1 72-kDa protein (CR208) or greatly reduced levels of IE2 86-kDa (IE2 86) protein (IE2 86ΔSX-EGFP). At a high multiplicity of infection, the IE1 deletion mutant is comparable to the wild type with respect to inhibition of HMGA2. In contrast, the IE2 86ΔSX-EGFP mutant does not significantly repress HMGA2 expression, suggesting that IE2 86 is involved in the regulation of this gene. Cyclin A expression is also induced in cells infected with this mutant virus. Since HMGA2 is important for cell proliferation and differentiation, particularly during embryogenesis, it is possible that the repression of HMGA2 expression during fetal development could contribute to the specific birth defects in HCMV-infected neonates. |
| تدمد: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.01300-06 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4e7f11ea0046d6ce11b05b820c80ba08 https://doi.org/10.1128/jvi.01300-06 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4e7f11ea0046d6ce11b05b820c80ba08 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10985514 0022538X |
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| DOI: | 10.1128/jvi.01300-06 |