Elke Mühlberger, Ph.D.

Associate Professor of Microbiology
Associate Director, Biomolecule Production Core, NEIDL Institute

Diploma in Biology    Philipps University, Marburg, Germany
Ph.D.                    Philipps University, Marburg, Germany

Ebola and Marburg virus, the only members of the filovirus family, are causative agents of viral hemorrhagic fever. With mortality rates as high as 90%, these viruses represent some of the most deadly human pathogens. We are interested in identifying virus- and cell-specific factors that contribute to virulence and pathogenicity of these viruses.

With regard to the virus-specific determinants, we are mainly interested in the filovirus replication machinery. Filoviruses belong to the group of nonsegmented negative-sense RNA viruses. The viral genome is replicated and transcribed by the virus-encoded RNA-dependent RNA polymerase complex. Our working hypothesis is based on the idea that high replication efficiency may be a prerequisite for high virulence. According to this hypothesis, viral infection should be controlled by the infected host if the replication efficiency is reduced. In order to compare the replication and transcription efficiency of filovirus species that differ in their pathogenicity, we have established minigenome systems for the highly pathogenic Ebola virus species Zaire, the less pathogenic Ebola virus species Reston as well as for Marburg virus. These systems are used for detailed investigation of cis-acting signals on the RNA genome and for structure-function analyses of the viral proteins involved in replication and transcription. Minigenome systems are useful tools to investigate the filoviral replication cycle under low biosafety level conditions.

A second topic of our investigations involves filovirus-host interaction. As many other viruses, filoviruses have evolved various mechanisms to evade the early innate immune response. We are interested to identify cellular targets of filovirus antagonists. These studies include regulation of IFN-mediated pathways, regulation of apoptotic processes and regulation of proinflammatory responses in infected cells.

Together, these investigations will provide a better understanding of how filoviruses evade or modulate cellular antiviral mechanisms and will help to develop antiviral countermeasures.

Representative Publications

  1. Habjan, M., Andersson, I., Klingström, J., Schümann, M., Martin, A., Zimmermann, P., Wagner, V., Pichlmair, A., Schneider, U., Mühlberger, E., Mirazimi, A., and Weber, F. 2008. Processing of genome 5’ termini as a strategy of negative-strand RNA viruses to avoid RIG-I-dependent interferon induction. PLoS ONE 3(4):e2032.
  2. Mühlberger, E. 2007. Filovirus replication and transcription. Future Virology 2: 205-215. (Review)
  3. Enterlein, S., Volchkov, V., Weik, M., Kolesnikova, L., Volchkova, V., Klenk, H.-D., and Mühlberger, E. 2006. Rescue of recombinant Marburg virus from cDNA is dependent on the nucleocapsid protein VP30. J. Virol. 80: 1038-1043.
  4. Kash, J. C.*, Mühlberger, E.*, Carter, V., Grosch, M., Proll, S., Thomas, M., Weber, F., Klenk, H.-D., and Katze, M. G. 2006. Global suppression of the host anti-viral response by Ebola and Marburg viruses. J. Virol. 80: 3009-3020.
    *  Equal contribution.
  5. Enterlein, S., Warfield, K. L., Swenson, D. L., Stein, D. A., Smith, J. L., Gamble, C. S., Kroeker, A. D., Iversen, P. L., Bavari, S., and Mühlberger, E. 2006. VP35 knockdown inhibits ebolavirus amplification and protects against lethal infection in mice. Antimicrob. Agents Chemother. 50: 984-993.
  6. Weik, M., Enterlein, S., Schlenz, K., and Mühlberger, E. 2005. The Ebola virus genomic replication promoter is bipartite and follows the rule of six. J. Virol. 79: 10660-10671.
  7. Boehmann, Y., Enterlein, S., Randolf, A, and Mühlberger, E. 2005. A reconstituted replication and transcription system for Ebola virus Reston and comparison with Ebola virus Zaire. Virology 332: 406-417.
  8. Modrof, J., Becker, S., and Mühlberger, E. 2003. The Ebola virus transcription activator VP30 is a zinc-binding protein. J. Virol. 77: 3334-3338.
  9. Weik, M., Modrof, J., Klenk, H.-D., Becker, S., and Mühlberger, E. 2002. Ebola virus VP30-mediated transcription is regulated by RNA secondary structure formation. J. Virol. 76: 8532-8539.
  10. Volchkov, V. E., Volchkova, V. A., Mühlberger, E., Kolesnikova, L. V., Weik, M., Dolnik, O., and Klenk, H.-D. 2001. Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity. Science 291: 1965-1969.
  11. Basler, C. F., Wang, X., Mühlberger, E., Volchkov, V., Paragas, J., Klenk, H.-D., Garcia-Sastre, A., and Palese, P. 2000. The Ebola virus VP35 protein functions as a type I IFN antagonist. Proc. Natl. Acad. Sci. U S A 97:12289-12294.

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Primary teaching affiliate
of BU School of Medicine