TY  - JOUR
A1  - Avota, Elita
A1  - Bodem, Jochen
A1  - Chithelen, Janice
A1  - Mandasari, Putri
A1  - Beyersdorf, Niklas
A1  - Schneider-Schaulies, Jürgen
T1  - The Manifold Roles of Sphingolipids in Viral Infections
JF  - Frontiers in Physiology
N2  - Sphingolipids are essential components of eukaryotic cells. In this review, we want to exemplarily illustrate what is known about the interactions of sphingolipids with various viruses at different steps of their replication cycles. This includes structural interactions during entry at the plasma membrane or endosomal membranes, early interactions leading to sphingolipid-mediated signal transduction, interactions with internal membranes and lipids during replication, and interactions during virus assembly and budding. Targeted interventions in sphingolipid metabolism – as far as they can be tolerated by cells and organisms – may open novel possibilities to support antiviral therapies. Human immunodeficiency virus type 1 (HIV-1) infections have intensively been studied, but for other viral infections, such as influenza A virus (IAV), measles virus (MV), hepatitis C virus (HCV), dengue virus, Ebola virus, and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), investigations are still in their beginnings. As many inhibitors of sphingolipid metabolism are already in clinical use against other diseases, repurposing studies for applications in some viral infections appear to be a promising approach.
KW  - sphingolipid
KW  - ceramide
KW  - sphingosine-1-phosphate
KW  - plasma membrane
KW  - virus entry
KW  - virus replication
KW  - virus budding
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246975
SN  - 1664-042X
VL  - 12
ER  - 
TY  - JOUR
A1  - Lambour, Benjamin
A1  - Glenz, René
A1  - Forner, Carmen
A1  - Krischke, Markus
A1  - Mueller, Martin J.
A1  - Fekete, Agnes
A1  - Waller, Frank
T1  - Sphingolipid long-chain base phosphate degradation can be a rate-limiting step in long-chain base homeostasis
JF  - Frontiers in Plant Science
N2  - Sphingolipid long-chain bases (LCBs) are building blocks for membrane-localized sphingolipids, and are involved in signal transduction pathways in plants. Elevated LCB levels are associated with the induction of programmed cell death and pathogen-derived toxin-induced cell death. Therefore, levels of free LCBs can determine survival of plant cells. To elucidate the contribution of metabolic pathways regulating high LCB levels, we applied the deuterium-labeled LCB D-erythro-sphinganine-d7 (D7-d18:0), the first LCB in sphingolipid biosynthesis, to Arabidopsis leaves and quantified labeled LCBs, LCB phosphates (LCB-Ps), and 14 abundant ceramide (Cer) species over time. We show that LCB D7-d18:0 is rapidly converted into the LCBs d18:0P, t18:0, and t18:0P. Deuterium-labeled ceramides were less abundant, but increased over time, with the highest levels detected for Cer(d18:0/16:0), Cer(d18:0/24:0), Cer(t18:0/16:0), and Cer(t18:0/22:0). A more than 50-fold increase of LCB-P levels after leaf incubation in LCB D7-d18:0 indicated that degradation of LCBs via LCB-Ps is important, and we hypothesized that LCB-P degradation could be a rate-limiting step to reduce high levels of LCBs. To functionally test this hypothesis, we constructed a transgenic line with dihydrosphingosine-1-phosphate lyase 1 (DPL1) under control of an inducible promotor. Higher expression of DPL1 significantly reduced elevated LCB-P and LCB levels induced by Fumonisin B1, and rendered plants more resistant against this fungal toxin. Taken together, we provide quantitative data on the contribution of major enzymatic pathways to reduce high LCB levels, which can trigger cell death. Specifically, we provide functional evidence that DPL1 can be a rate-limiting step in regulating high LCB levels.
KW  - sphingolipid
KW  - long-chain base
KW  - plant sphingolipid metabolism
KW  - cell death
KW  - metabolic flux analysis
KW  - dihydrosphingosine-1-phosphate lyase
KW  - LC–MS/MS
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-277679
SN  - 1664-462X
VL  - 13
ER  -