Morphogenesis and transport of filovirus nucleocapsids

 

Prof. Dr. Stephan Becker

Institut für Virologie
Hans-Meerwein-Str 2
35043 Marburg

Tel.: 06421-28 66253

E-mail: Becker@staff.uni-marburg.de
www.uni-marburg.de/fb20/virologie

 

Project description  

The highly pathogenic filoviruses, Marburg virus and Ebola virus, replicate in the cytoplasm of infected cells and induce the formation of inclusions in the perinuclear region. The inclusions represent accumulations of newly formed nucleocapsids and presumably sites of replication and transcription. In the vicinity of the inclusions accumulations of mitochondria, lipid droplets and ribosomes are frequently detected and membranes of the rough ER seem to surround these MARV-induced intracytoplasmic microcompartments (Fig. 1). In the presence of the MARV matrix protein VP40, mature nucleocapsids are released from the inclusions and transported to the plasma membrane where they are enveloped and released. It is not understood in detail, how the inclusions and nucleocapsids are formed. It is also unclear, which cellular pathways are used to transport the nucleocapsids to the plasma membrane and how this process is regulated. We propose to investigate (i) the spatial organization of the inclusions and their adjacencies, (ii) the structure and formation of nucleocapsids in the cytoplasm, (iii) transport of nucleocapsids to the plasma membrane and (iv) interaction of the major nucleocapsid protein NP with cytoplasmic transport proteins.

 

 

Staff

Dr. Olga Dolnik (Co-project leader)
Dr. Hosam Shams-Eldin (Senior Postdoc)
Dirk Becker (Technical Assistant)
Nadine Biedenkopf (PhD Student)
Anne Brüggemann (PhD Student)

Publications since 2007

Becker, S., 2007. Fighting filoviruses. Expert Review of Vaccines 6, 1-3.

DiCarlo, A., Moller, P., Lander, A., Kolesnikova, L., Becker, S., 2007. Nucleocapsid formation and RNA synthesis of Marburg virus is dependent on two coiled coil motifs in the nucleoprotein. Virol J 4, 105.

Dolnik, O., Kolesnikova, L., Becker, S., 2008. Filoviruses: Interactions with the host cell. Cell Mol Life Sci 65, 756-776.

Dolnik, O., Kolesnikova, L., Stevermann, L., Becker, S., 2010. Tsg101 is recruited by a late domain of the nucleocapsid protein to support budding of Marburg virus-like particles. J Virol 84, 7847-7856.

Groseth, A., Hoenen, T., Alimonti, J.B., Zielecki, F., Ebihara, H., Theriault, S., Strher, U., Becker, S., Feldmann, H., 2007. In Vitro Evaluation of Antisense RNA Efficacy against Filovirus Infection, by Use of Reverse Genetics. J Infect Dis 196, S382-S389.

Groseth, A., Wolff, S., Strecker, T., Hoenen, T., Becker, S., 2010. Efficient budding of the tacaribe virus matrix protein z requires the nucleoprotein. J Virol 84, 3603-3611.

Hartlieb, B., Muziol, T., Weissenhorn, W., Becker, S., 2007. Crystal structure of the C-terminal domain of Ebola virus VP30 reveals a role in transcription and nucleocapsid association. Proc Natl Acad Sci U S A 104, 624-629.

Hoenen, T., Biedenkopf, N., Zielecki, F., Jung, S., Groseth, A., Feldmann, H., Becker, S., 2010a. Oligomerization of Ebola virus VP40 is essential for particle morphogenesis and regulation of viral transcription. J Virol.

Hoenen, T., Jung, S., Herwig, A., Groseth, A., Becker, S., 2010b. Both matrix proteins of Ebola virus contribute to the regulation of viral genome replication and transcription. Virology.

Hoenen, T., Kolesnikova, L., Becker, S., 2007. Recent advances in filovirus- and arenavirus-like particles. Future Virology 2, 193.
Kolesnikova, L., Bohil, A.B., Cheney, R.E., Becker, S., 2007a. Budding of Marburgvirus is associated with filopodia. Cell Microbiol 9, 939-951.

Kolesnikova, L., Ryabchikova, E., Shestopalov, A., Becker, S., 2007b. Basolateral Budding of Marburg Virus: VP40 Retargets Viral Glycoprotein GP to the Basolateral Surface. J Infect Dis 196, S232-S236.

Kolesnikova, L., Strecker, T., Morita, E., Zielecki, F., Mittler, E., Crump, C., Becker, S., 2009. Vacuolar protein sorting pathway contributes to the release of Marburg virus. J Virol 83, 2327-2337.

Krahling, V., Dolnik, O., Kolesnikova, L., Schmidt-Chanasit, J., Jordan, I., Sandig, V., Gunther, S., Becker, S., 2010. Establishment of fruit bat cells (Rousettus aegyptiacus) as a model system for the investigation of filoviral infection. PLoS Negl Trop Dis 4, e802.

Lucht, A., Formenty, P., Feldmann, H., Gtz, M., Leroy, E., Bataboukila, P., Grolla, A., Feldmann, F., Wittmann, T., Campbell, P., Atsangandoko, C., Boumandoki, P., Finke, E.-J., Miethe, P., Becker, S., Grunow, R., 2007. Development of an Immunofiltration-Based Antigen-Detection Assay for Rapid Diagnosis of Ebola Virus Infection. J Infect Dis 196, S184-S192.

Martinez, M.J., Biedenkopf, N., Volchkova, V., Hartlieb, B., Alazard-Dany, N., Reynard, O., Becker, S., Volchkov, V., 2008. Role of Ebola virus VP30 in transcription reinitiation. J Virol 82, 12569-12573.

Marzi, A., Möller, P., Hanna, S.L., Harrer, T., Eisemann, J., Steinkasserer, A., Becker, S., Baribaud, F., Pöhlmann, S., 2007. Analysis of the Interaction of Ebola Virus Glycoprotein with DC-SIGN (Dendritic Cell-Specific Intercellular Adhesion Molecule 3-Grabbing Nonintegrin) and Its Homologue DC-SIGNR. J Infect Dis 196, S237-S246.

Mittler, E., Kolesnikova, L., Strecker, T., Garten, W., Becker, S., 2007. Role of the transmembrane domain of marburg virus surface protein GP in assembly of the viral envelope. J Virol 81, 3942-3948.

Muller, S., Moller, P., Bick, M.J., Wurr, S., Becker, S., Gunther, S., Kummerer, B.M., 2007. Inhibition of Filovirus Replication by the Zinc Finger Antiviral Protein. J. Virol. 81, 2391-2400.

Panning, M., Eickmann, M., Landt, O., Monazahian, M., Olschlager, S., Baumgarte, S., Reischl, U., Wenzel, J.J., Niller, H.H., Gunther, S., Hollmann, B., Huzly, D., Drexler, J.F., Helmer, A., Becker, S., Matz, B., Eis-Hubinger, A., Drosten, C., 2009. Detection of influenza A(H1N1)v virus by real-time RT-PCR. Euro Surveill 14.

Panning, M., Laue, T., lschlager, S., Eickmann, M., Becker, S., Raith, S., Courbot, M.-C.G., Nilsson, M., Gopal, R., Lundkvist, A., Caro, A.d., Brown, D., Meyer, H., Lloyd, G., Kmmerer, B.M., Gnther, S., Drosten, C., 2007. Diagnostic Reverse-Transcription Polymerase Chain Reaction Kit for Filoviruses Based on the Strain Collections of all European Biosafety Level 4 Laboratories. J Infect Dis 196, S199-S204.

Salditt, A., Koethe, S., Pohl, C., Harms, H., Kolesnikova, L., Becker, S., Schneider-Schaulies, S., 2010. Measles virus M protein-driven particle production does not involve the endosomal sorting complex required for transport (ESCRT) system. J Gen Virol 91, 1464-1472.

Voss, D., Pfefferle, S., Drosten, C., Stevermann, L., Traggiai, E., Lanzavecchia, A., Becker, S., 2009. Studies on membrane topology, N-glycosylation and functionality of SARS-CoV membrane protein. Virol J 6, 79.

Welsch, S., Kolesnikova, L., Krahling, V., Riches, J.D., Becker, S., Briggs, J.A., 2010. Electron tomography reveals the steps in filovirus budding. PLoS Pathog 6, e1000875.

Wenigenrath, J., Kolesnikova, L., Hoenen, T., Mittler, E., Becker, S., 2010. Establishment and application of an infectious virus-like particle system for Marburg virus. J Gen Virol 91, 1325-1334.