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Medical Microbiology and Immunology
Published in: Medical Microbiology and Immunology 3-4/2018

01-08-2018 | Original Investigation

Influence of sphingosine-1-phosphate signaling on HCMV replication in human embryonal lung fibroblasts

Authors: Anika Zilch, Christian Rien, Cynthia Weigel, Stefanie Huskobla, Brigitte Glück, Katrin Spengler, Andreas Sauerbrei, Regine Heller, Markus Gräler, Andreas Henke

Published in: Medical Microbiology and Immunology | Issue 3-4/2018

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Abstract

The human cytomegalovirus (HCMV) is a common pathogen, which causes severe or even deadly diseases in immunocompromised patients. In addition, congenital HCMV infection represents a major health concern affecting especially the lung tissue of the susceptible individuals. Antivirals are a useful strategy to treat HCMV-caused diseases. However, all approved drugs target viral proteins but significant toxicity and an increasing resistance against these compounds have been observed. In infected cells, numerous host molecules have been identified to play important roles during HCMV replication. Among others, HCMV infection depends on the presence of bioactive sphingolipids. In this study, the role of sphingosine-1-phosphate (S1P) signaling in HCMV-infected human embryonal lung fibroblasts (HELF) was analyzed. Viral replication depended on the functional activity of sphingosine kinases (SK). During SK inhibition, addition of extracellular S1P restored HCMV replication. Moreover, neutralization of extracellular S1P by anti-S1P antibodies decreased HCMV replication as well. While the application of FTY720 as an functional antagonist of S1P receptor (S1PR)1,3−5 signaling did not reduce HCMV replication significantly, JTE-013, an inhibitor of S1PR2, decreased viral replication. Furthermore, inhibition of Rac-1 activity reduced HCMV replication, whereas inhibition of the Rac-1 effector protein Rac-1-activated kinase 1 (PAK1) had no influence. In general, targeting S1P-induced pathways, which are essential for a successful HCMV replication, may represent a valuable strategy to develop new antiviral drugs.
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Metadata
Title
Influence of sphingosine-1-phosphate signaling on HCMV replication in human embryonal lung fibroblasts
Authors
Anika Zilch
Christian Rien
Cynthia Weigel
Stefanie Huskobla
Brigitte Glück
Katrin Spengler
Andreas Sauerbrei
Regine Heller
Markus Gräler
Andreas Henke
Publication date
01-08-2018
Publisher
Springer Berlin Heidelberg
Published in
Medical Microbiology and Immunology / Issue 3-4/2018
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI
https://doi.org/10.1007/s00430-018-0543-4

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