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Systems Biology of Virus-Host Interactions

Viruses rely on host cell processes for cell entry, replication and spread. This leads to complex interactions between viral and host genes and proteins, which we are only beginning to understand. Based on high-throughput RNAi screening data, time resolved measurements of viral replication, and life cell imaging, we aim to identifying unknown host factors, and integrate those into mathematical models of virus-host interactions during the viral life cycle. Ultimately, such models can be used to simulate infections in the computer, and study the effect of possible new antiviral compounds in silico.

Hepatitis C virus replication

Hepatitis C is a medically highly relevant infectious disease affecting more than 170 million people world wide. It is caused by the hepatitis C virus (HCV), which infects the liver cells of its host. After the initial infection, which is often asymptomatic, the infection becomes chronic in a large proportion of patients leading to chronic infection and serious liver diseases such as liver cirrhosis and cancer. Currently, there is no vaccine available and the standard-of-care medical therapy works only in some patients, depending among other factors on the specific viral genotype and genetic background of the patient. There is an urgent need to advance our understanding of HCV infections to develop novel medical treatment.

In close collaboration with Dr. Marco Binder from the department of Virology (AG Bartenschlager) at the University of Heidelberg, we are developing a mathematical model of hepatitis C virus replication in Huh-7 cells. Based on experimental data provided by our experimental partner, we aim at quantitatively describing virus replication, integrating host factors and host signaling triggered by the infection. Our ultimate aim is to integrate this model with models of immune response, and embed the intracellular model into a comprehensive multi-scale model of the full viral lifecycle, and its key interactions with the host. This is done using a combination of bioinformatics, statistical data analysis, machine learning and mathematical modeling.

Human Immunodeficiency Virus (HIV) Lifecycle Models

A second important RNA virus is HIV, the causative agent of AIDs. Like HCV, HIV is also an RNA virus, but in contrast to HCV, its RNA genome is reverse transcribed to DNA, which then integrates into the hosts genome.

We are developing quantitative mathematical models of the full HIV lifecycle, to quantitatively and dynamically study infection and viral replication of this important pathogen, and the effect of antiviral drugs.

Publications

  1. D. Clausznitzer, N. Sulaimanov, M. Binder, V. Lohmann, R. Bartenschlager, L. Kaderali (2011). Systembiologie der Hepatitis C-Virus-Wirts-Interaktionen. Laborwelt 6:13-15.
  2. J. Gentzsch, B. Hinkelmann, L. Kaderali, H. Irschik, R. Jansen, F. Sasse, R. Frank, T. Pietschmann (2011). Hepatitis C virus complete life cycle screen for identification of small molecules with pro- or antiviral activity. Antiviral Research 89(2):136-48.
  3. S. Reiss, I. Rebhan, P. Backes, I. Romero-Brey, H. Erfle, P. Matula, L. Kaderali, M. Pönisch, H. Blankenburg, M.-S. Hiet, T. Longerich, S. Diehl, F. Ramirez, T. Balla, K. Rohr, A. Kaul, S. Bühler, R. Pepperkok, T. Lengauer, M. Albrecht, R. Eils, P. Schirmacher, V. Lohmann, R. Bartenschlager (2011) Recruitment and activation of a lipid kinase by NS5A of the hepatitis C virus is essential for integrity of the membranous replication compartment. Cell Host & Microbe 9(1):32-45.
  4. A, Suratanee, I. Rebhan, P. Matula, A. Kumar, L. Kaderali, K. Rohr, R. Bartenschlager, R. Eils, R. König (2010). Detecting host factors involved in virus infection by observing the clustering of infected cells in siRNA screening images. Bioinformatics 26:i653-i658, doi:10.1093/bioinformatics/btq398.
  5. K. Börner, J. Hermle, C. Sommer, N. P. Brown, B. Knapp, B. Glass, J. Kunkel, G. Torralba, J. Reymann, N. Beil, J. Beneke, R. Pepperkok, R. Schneider, T. Ludwig, M. Hausmann, F. Hamprecht, H. Erfle, L. Kaderali, H.-G. Kräusslich, M. J. Lehmann (2010) From experimental setup to bioinformatics: An RNAi screening platform to identify host factors and potential cellular networks involved in HIV-1 replication, Biotechnology Journal, 5(1), 39-49.
  6. S. Geuenich, L. Kaderali, I. Allespach, S. Sertel, O. T. Keppler (2009). Biological Signature Characterisitics of Primary Isolates from HIV-1 Group O in the ex vivo Human Tonsil Histoculture. Journal of Virology, 83(20), 10494-10503, doi:10.1128/JVI.00928-09.