Our group is interested in the interaction of cytomegaloviruses (CMV) with their host cells. Which are the viral factors that allow CMV to replicate in specific host cells? How does the virus influence the function of host cells? Based on the knowledge of virus-cell interactions we are going to develop herpesviral vectors for vaccination and gene therapy.

Research summary

Human Cytomegalovirus (HCMV) is a widespread pathogen, with 50-80% of the population being infected. Primary infection is usually asymptomatic, but life-threatening disease can occur in immunocompromised patients, especially in transplant recipients or AIDS patients. HCMV infection is also the most frequent viral infection during pregnancy, often leading to malformation of the fetus, typically resulting in deafness or mental retardation. In order to make cytomegalovirus functions amenable to efficient genetic analysis we cloned the genomes of mouse and human cytomegalovirus as bacterial artificial chromosomes (BAC) in E.coli. Now, we can manipulate the viral genomes by the powerful techniques of bacterial genetics and generate viral mutants by transfection of the mutated BACs into permissive eukaryotic cells (Messerle et al., 1997; Borst et al., 1999). Analysis of the phenotypes of the mutant viruses allows the linkage of viral functions to genes. During their long co-evolution with their specific hosts, cytomegaloviruses have developed various strategies to modulate or even evade the host immune system. Many viral functions enabling the viruses to exploit the host cells for their own ends are poorly understood or remain elusive. Using the genetic approach, we have started to identify and characterize genes of the mouse CMV (MCMV) that interfere with the function of antigen-presenting cells (Loewendorf et al., 2004). We also aim to identify viral factors that determine the tropism of CMV for epithelial cells, a cell type that may be important for CMV transmission. Due to its tropism for hematopoietic progenitor cells, CMV is a promising vector candidate for gene transfer into cells of the hematopoietic system. We have constructed a CMV amplicon vector which provides a unique capacity for the transfer of foreign genes (Borst and Messerle, 2003). With the intention of optimizing the replication of this CMV vector, we studied the genetic elements required for the efficient replication of the viral genome (Borst and Messerle, 2005). Further knowledge of viral genes modulating the functions of host cells will allow the construction of vectors for vaccination and for specific applications in gene transfer protocols. Viruses can be tailored for specific replication in tumor cells leading to destruction of tumor cells. Due to its tropism for neuronal cells, Herpes simplex virus type 1 offers a potential for virotherapy of brain tumors. In collaboration with Dr. Söling (Medical School Halle) and Dr. Sodeik we are developing novel oncolytic Herpes simplex viruses and evaluating their potential for destruction of glioma tumors.

    +49 511 532 4320 fax:+49 511 532 8736| Messerle.Martin@MH-Hannover.De

    +49 511 532 4320 | Borst.Eva@MH-Hannover.De

    +49 511 532 4321 | Kay-Jackson.Penelope@MH-Hannover.De

    +49 511 532 4321 | Glass.Mandy@MH-Hannover.De

    +49 511 532 4321 | Muether.Nadine@MH-Hannover.De

    +49 511 532 4321 | Sengstake.Sarah@MH-Hannover.De

    +49 511 532 4321 | Steinbrueck.Lars@MH-Hannover.De

More Informations

The German Research Council (Deutsche Forschungsgemeinschaft) funds our research with a project grant (Me1102), a project of the SFB 587, and a joint research program of the Hannover Medical and Veterinary Schools (Graduiertenkolleg 745: Mucosal host-pathogen interactions). The development of oncolytic viruses is supported by the Wilhelm-Sander Foundation. Before our move to Hannover our research projects were supported by the NBL3-Program of the German Ministry of Education and Research (BMBF) and the Wilhelm-Roux-Program of the Medical School of the University of Halle-Wittenberg.

Messerle, M., Crnkovic, I., Ziegler, H., Hammerschmidt, W., Koszinowski, U.H. Cloning and mutagenesis of a herpesvirus genome as an infectious bacterial artificial chromosome. Proc. Natl. Acad. Sci. U.S.A. 1997, 94:14759-63.

Borst, E., Hahn, G., Koszinowski, U.H., Messerle, M. Cloning of the human cytomegalovirus (HCMV) genome as an infectious bacterial artificial chromosome in Escherichia coli: a new approach for construction of HCMV mutants. J. Virol. 1999, 73:8320-9.

Krmpotic, A., Messerle, M., Crnkovic-Mertens, I., Polic, B., Jonjic, S., Koszinowski, U.H. The immunoevasive function encoded by the mouse cytomegalovirus gene m152 protects the virus against T cell control in vivo. J. Exp. Med. 1999, 190:1285-95.