Knoblach, Theresa and Grandel, Benedikt and Seiler, Jana and Nevels, Michael and Paulus, Christina (2011) Human Cytomegalovirus IE1 Protein Elicits a Type II Interferon-Like Host Cell Response That Depends on Activated STAT1 but Not Interferon-gamma. PLOS PATHOGENS, 7 (4): e1002016. ISSN 1553-7366, 1553-7374
Full text not available from this repository. (Request a copy)Abstract
Human cytomegalovirus (hCMV) is a highly prevalent pathogen that, upon primary infection, establishes life-long persistence in all infected individuals. Acute hCMV infections cause a variety of diseases in humans with developmental or acquired immune deficits. In addition, persistent hCMV infection may contribute to various chronic disease conditions even in immunologically normal people. The pathogenesis of hCMV disease has been frequently linked to inflammatory host immune responses triggered by virus-infected cells. Moreover, hCMV infection activates numerous host genes many of which encode pro-inflammatory proteins. However, little is known about the relative contributions of individual viral gene products to these changes in cellular transcription. We systematically analyzed the effects of the hCMV 72-kDa immediate-early 1 (IE1) protein, a major transcriptional activator and antagonist of type I interferon (IFN) signaling, on the human transcriptome. Following expression under conditions closely mimicking the situation during productive infection, IE1 elicits a global type II IFN-like host cell response. This response is dominated by the selective up-regulation of immune stimulatory genes normally controlled by IFN-gamma and includes the synthesis and secretion of pro-inflammatory chemokines. IE1-mediated induction of IFN-stimulated genes strictly depends on tyrosine-phosphorylated signal transducer and activator of transcription 1 (STAT1) and correlates with the nuclear accumulation and sequence-specific binding of STAT1 to IFN-gamma-responsive promoters. However, neither synthesis nor secretion of IFN-gamma or other IFNs seems to be required for the IE1-dependent effects on cellular gene expression. Our results demonstrate that a single hCMV protein can trigger a proinflammatory host transcriptional response via an unexpected STAT1-dependent but IFN-independent mechanism and identify IE1 as a candidate determinant of hCMV pathogenicity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; IMMEDIATE-EARLY PROTEINS; SIMPLEX-VIRUS TYPE-1; LONG TERMINAL REPEAT; NEUTROPHIL TRANSENDOTHELIAL MIGRATION; HEMATOPOIETIC PROGENITOR CELLS; INTERLEUKIN-6 GENE-EXPRESSION; LATENT HUMAN CYTOMEGALOVIRUS; INFECTED ENDOTHELIAL-CELLS; LOW-MULTIPLICITY INFECTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Jun 2020 05:03 |
| Last Modified: | 23 Jun 2020 05:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20992 |
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