Efficient Human Cytomegalovirus Replication in Primary Endothelial Cells Is SOCS3 Dependent
| Autor: | Gerburg M. Wulf, Olmo Sonzogni, Roberto F. Speck, Nicolas J. Mueller, Anne-Laure Millard, Aline Taveira, Li Duo, Mårten K J Schneider |
|---|---|
| Přispěvatelé: | University of Zurich, Sonzogni, Olmo |
| Rok vydání: | 2018 |
| Předmět: |
Human cytomegalovirus
viruses medicine.medical_treatment Cytomegalovirus 610 Medicine & health 030312 virology Virus Replication 10234 Clinic for Infectious Diseases 03 medical and health sciences Suppressor of Cytokine Signaling 1 Protein Virology medicine Humans STAT1 SOCS3 Gene Silencing STAT2 Phosphorylation RNA Small Interfering Lung Cells Cultured 030304 developmental biology 0303 health sciences Immunity Cellular biology Suppressor of cytokine signaling 1 digestive oral and skin physiology Endothelial Cells 2725 Infectious Diseases Transfection medicine.disease Molecular biology Infectious Diseases Cytokine STAT1 Transcription Factor Suppressor of Cytokine Signaling 3 Protein 2406 Virology biology.protein STAT protein Signal Transduction |
| Zdroj: | Intervirology. 62(2) |
| ISSN: | 1423-0100 |
| Popis: | Background: In immunocompromised patients, human cytomegalovirus (HCMV) infection is a major cause of morbidity and mortality. Suppressor of cytokine signaling (SOCS) proteins are very potent negative regulators of the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. We hypothesized that HCMV exploits SOCS1 and/or SOCS3 to its advantage. Methods: All experiments were carried out with primary human lung-derived microvascular endothelial cells (HMVEC). SOCS1 and SOCS3 were silenced by transfecting the cells with siRNA. HCMV was propagated and titered on human lung-derived fibroblasts MRC5. Real-time PCR and Western blot were used to detect mRNA and protein levels, respectively. Results: The data presented show that an efficient replication of HCMV in HMVEC is dependent on SOCS3 protein. Time course analysis revealed an increase in SOCS3 protein levels in infected cells. Silencing of SOCS3 (siSOCS3) resulted in inhibition of viral immediate early, early, and late antigen production. Consistently, HCMV titers produced by siSOCS3 cultures were significantly decreased when compared to control transfected cultures (siCNTRs). STAT1 and STAT2 phosphorylation was increased in siSOCS3-infected cells when compared to siCNTR-treated cells. Conclusion: These findings indicate the implication of SOCS3 in the mechanism of HCMV-mediated control of cellular immune responses. |
| Databáze: | OpenAIRE |
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