B6 P: Identification of antiviral targets in lipid metabolism

Principal Investigator:

Prof. Dr. Eva Herker

Institut für Virologie
Philipps-Universität Marburg
Hans-Meerwein-Str. 2
35043 Marburg
Tel.: +49 (0)6421-28-64525
E-Mail: eva.herker(at)uni-marburg(dot)de

Project description:

The human pathogenic flaviviruses Dengue (DENV), Yellow Fever (YFV), Zika (ZIKV), West Nile (WNV) and tick-borne encephalitis virus (TBEV) cause acute infections with severe complications. Fundamental steps in flavivirus replication are closely linked to cellular lipids. These include, among other things, membrane reorganizations for the formation of replication vesicles or capsid envelopment. Flaviviruses alter the lipid composition of the host cell, and the activity of various lipid-metabolizing enzymes is essential for successful replication. For this reason, enzymes from different lipid metabolism pathways represent interesting targets for (pan-) antiflaviviral therapy. However, it has not yet been clarified in detail whether the above-mentioned flaviviruses are dependent on different or similar branches of lipid metabolism.

Immunofluorescence microscopy of cells infected with different flaviviruses; red: viral E protein; green: lipid droplets.

Scientific goal:

The project aims to identify antiviral targets in the cellular lipid metabolism. The role of various key enzymes in de novo fatty acid and cholesterol biosynthesis, in phospholipid and neutral lipid metabolism, and of lipid remodeling enzymes in flavivirus replication is analyzed using an shRNA-based screen. In addition, various inhibitors are tested. The results are validated in different cell types and the molecular mechanisms are examined in detail


DRUID Collaboration partners:

B1 Diederich/Kolb, D1 Böttcher-Friebertshäuser/Steinmetzer, E7P Krijnse-Locker, E4 Spengler

References B6P: Herker et al. (2010) Nat Med 16: 1295 2. Harris et al. (2011) J Biol Chem 286: 42615 3. Herker et al. (2012) J Biol Chem 287: 2280 4. Rosch et al. (2016) Cell Rep 16: 3219 5. Hofmann et al. (2018) Biochim Biophys Acta Mol Cell Biol Lipids 1863: 1041 6. Schobel et al. (2018) Sci Rep 8: 3893 7. Lassen et al. (2019) J Cell Sci 132: jcs.217042 8. Bley et al. (2020) Int J Mol Sci 21:  9. Herker et al. (2021) Trends Cell Biol 31: 345 10. Nguyen-Dinh et al. (2021) Cells 10: 2407