Function of lipid droplets in replication and pathogenesis of neurotropic flaviviruses

Research area: Virus-host Interaction

Viruses rely on host lipid metabolic pathways for replication. Lipid droplets are the main cellular storage organelles of neutral lipids and central hubs of lipid trafficking. The Herker group investigates the function of lipid droplets in virus infection and pathogenesis and how viruses rewire cellular metabolic pathways for successful replication. Capsid proteins from hepatitis C virus (HCV) and different flavivirus family members localize to lipid droplets and, depending on cell types and viruses, lipid droplet accumulation and degradation have been observed in infected cells. However, it is currently unknown, how neurotropic flaviviruses interact with the intricate lipid metabolism of brain cells. This project aims to i) characterize host cell lipid droplets after expression of the capsid protein C or during West Nile virus (WNV), Zika virus (ZIKV), and tick-borne encephalitis virus (TBEV) infection in different cell types, such as neuron and astrocyte cell lines, human neurons and astrocytes differentiated from stem cells, and murine primary cells, ii) determine if WNV, ZIKV, and TBEV infection is inhibited by interference with lipid droplet formation and/or lipid mobilization, and iii) elucidate if virus-induced pathogenic effects are in part due to metabolic disturbance.

Project-related publications of the investigator:

  • Herker E, Vieyres G, Beller M, Krahmer N, Bohnert M. 2021. Lipid Droplet Contact Sites in Health and Disease. Trends Cell Biol 31:345-358.
  • Bley H, Schobel A, Herker E. 2020. Whole Lotta Lipids-from HCV RNA Replication to the Mature Viral Particle. Int J Mol Sci 21.
  • Lassen S, Gruttner C, Nguyen-Dinh V, Herker E. 2019. Perilipin-2 is critical for efficient lipoprotein and hepatitis C virus particle production. J Cell Sci 132.
  • Schobel A, Rosch K, Herker E. 2018. Functional innate immunity restricts Hepatitis C Virus infection in induced pluripotent stem cell-derived hepatocytes. Sci Rep 8:3893.
  • Hofmann S, Krajewski M, Scherer C, Scholz V, Mordhorst V, Truschow P, Schobel A, Reimer R, Schwudke D, Herker E. 2018. Complex lipid metabolic remodeling is required for efficient hepatitis C virus replication. Biochim Biophys Acta Mol Cell Biol Lipids 1863:1041-1056.
  • Rosch K, Kwiatkowski M, Hofmann S, Schobel A, Gruttner C, Wurlitzer M, Schluter H, Herker E. 2016. Quantitative Lipid Droplet Proteome Analysis Identifies Annexin A3 as a Cofactor for HCV Particle Production. Cell Rep 16:3219-3231.
  • Eggert D, Rosch K, Reimer R, Herker E. 2014. Visualization and analysis of hepatitis C virus structural proteins at lipid droplets by super-resolution microscopy. PLoS One 9:e102511.
  • Camus G, Schweiger M, Herker E, Harris C, Kondratowicz AS, Tsou CL, Farese RV, Jr., Herath K, Previs SF, Roddy TP, Pinto S, Zechner R, Ott M. 2014. The hepatitis C virus core protein inhibits adipose triglyceride lipase (ATGL)-mediated lipid mobilization and enhances the ATGL interaction with comparative gene identification 58 (CGI-58) and lipid droplets. J Biol Chem 289:35770-80.
  • Vogt DA, Camus G, Herker E, Webster BR, Tsou CL, Greene WC, Yen TS, Ott M. 2013. Lipid droplet-binding protein TIP47 regulates hepatitis C Virus RNA replication through interaction with the viral NS5A protein. PLoS Pathog 9:e1003302.
  • Camus G, Herker E, Modi AA, Haas JT, Ramage HR, Farese RV, Jr., Ott M. 2013. Diacylglycerol acyltransferase-1 localizes hepatitis C virus NS5A protein to lipid droplets and enhances NS5A interaction with the viral capsid core. J Biol Chem 288:9915-9923.
  • Herker E, Ott M. 2012. Emerging role of lipid droplets in host/pathogen interactions. J Biol Chem 287:2280-7.
  • Herker E, Ott M. 2011. Unique ties between hepatitis C virus replication and intracellular lipids. Trends Endocrinol Metab 22:241-8.
  • Harris C, Herker E, Farese RV, Jr., Ott M. 2011. Hepatitis C virus core protein decreases lipid droplet turnover: a mechanism for core-induced steatosis. J Biol Chem 286:42615-42625.
  • Herker E, Harris C, Hernandez C, Carpentier A, Kaehlcke K, Rosenberg AR, Farese RV, Jr., Ott M. 2010. Efficient hepatitis C virus particle formation requires diacylglycerol acyltransferase-1. Nat Med 16:1295-8.