The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Human Cytomegalovirus Inhibits Major Histocompatibility Complex Class II Expression By Disruption of the Jak/Stat Pathway
Open accessAbstract
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that is able to persist for decades in its host. HCMV has evolved protean countermeasures for anti-HCMV cellular immunity that facilitate establishment of persistence. Recently it has been shown that HCMV inhibits interferon γ (IFN-γ)–stimulated MHC class II expression, but the mechanism for this effect is unknown. IFN-γ signal transduction (Jak/Stat pathway) and class II transactivator (CIITA) are required components for IFN-γ–stimulated MHC class II expression. In this study, we demonstrate that both a clinical isolate and a laboratory strain of HCMV inhibit inducible MHC class II expression at the cell surface and at RNA level in human endothelial cells and fibroblasts. Moreover, reverse transcriptase polymerase chain reaction and Northern blot analyses demonstrate that neither CIITA nor interferon regulatory factor 1 are upregulated in infected cells. Electrophoretic mobility shift assays reveal a defect in IFN-γ signal transduction, which was shown by immunoprecipitation to be associated with a striking decrease in Janus kinase 1 (Jak1) levels. Proteasome inhibitor studies with carboxybenzyl-leucyl-leucyl-leucine vinyl sulfone suggest an HCMV-associated enhancement of Jak1 protein degradation. This is the first report of a mechanism for the HCMV-mediated disruption of inducible MHC class II expression and a direct virus-associated alteration in Janus kinase levels. These findings are yet another example of the diverse mechanisms by which HCMV avoids immunosurveillance and establishes persistence.
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Cited by
STATs: transcriptional control and biological impact
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Antiviral Actions of Interferons
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Viral Subversion of the Immune System
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SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses
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Metadata
- Authors
- Miller, D. M., Rahill, B. M., Boss, J. M., Lairmore, M. D., Durbin, J. E., Waldman, J. W., & Sedmak, D. D.
- Venue
- The Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 1998-03-02
- Volume
- 187
- Issue
- 5
- Pages
- 675-683
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2057272534
- Cited by
- 337
- References
- 41
- FWCI
- 29.18
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Miller, D. M., Rahill, B. M., Boss, J. M., Lairmore, M. D., Durbin, J. E., Waldman, J. W., & Sedmak, D. D. (1998). Human Cytomegalovirus Inhibits Major Histocompatibility Complex Class II Expression By Disruption of the Jak/Stat Pathway. The Journal of Experimental Medicine. https://doi.org/10.1084/jem.187.5.675
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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