Cytomegalovirus (CMV) research group
The lab focuses on the regulation of gene expression and RNA biology. In terms of viruses we dissect the regulation of herpesviral RNA expression. On the cellular side we are interested in non-coding mutations causing various human diseases. Both areas follow our central idea: A deeper knowledge of both viral gene expression and the pathomechanisms of non-coding mutations will advance our understanding of cellular processes.
Human cytomegalovirus (HCMV) is a widespread pathogen, with 50-80% of the population being infected. Primary infection in healthy persons 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, with a typically manifestation being deafness.
In order to make cytomegalovirus functions amenable to efficient genetic analysis, many years ago we cloned the genomes of mouse and human cytomegalovirus as bacterial artificial chromosomes (BAC) in E.coli (Messerle et al., 1997; Borst et al., 1999). This allows us to manipulate the viral genomes by the powerful techniques of bacterial genetics and to generate viral mutants upon transfection of permissive eukaryotic cells with mutated BACs. By analyzing the phenotypes of the mutant viruses viral functions can be assigned to specific genes.
During the long co-evolution with their hosts, CMVs have developed various strategies to modulate important pathways of infected cells. Many viral functions enabling the viruses to exploit the host cells for their own ends are poorly understood or remain elusive. We are interested in the interaction of cytomegaloviruses with their host cells and the modulation of the immune response, particularly during persisting infection. Based on the knowledge of virus-cell interactions we test vaccination concepts against HCMV using suitable mutants. Not least, we investigate how infected cells support the assembly and the maturation of new CMV particles and aim at the development of antivirals disrupting the viral life cycle.
- Prof. rer. nat. Martin Messerle
Medizinische Hochschule Hannover (Hannover Medical School)
Institute of Virology, OE5230
Phone +49 511 532 4320
Departmental Secretary +49 511 532 6736
Laboratory +49 511 532 4321
Dr. Messerle studied biology at the University of Tübingen and graduated in 1986. He obtained his doctorate (Dr. rer. nat.) in 1990 with a dissertation on the analysis of the structure of the immediate-early (IE) genes and of the functional and immunological properties of the IE proteins of mouse cytomegalovirus. Following several years as a postdoc and scientific assistant at the universities of Ulm, Freiburg, Heidelberg and Munich, he obtained his "Habilitation" in Experimental Virology at the Ludwig-Maximilians-University of Munich in 2002. In 1997 he stayed as a guest scientist at the Scripps Research Institute in La Jolla, CA. In 2001 he got a position as an assistant professor at the Medical Faculty of the University of Halle-Wittenberg and was head of the Virus-Cell-Interaction Unit. He was appointed as Associate Professor of Molecular Virology at the Hannover Medical School in Jan. 2005.
Borst, Eva Maria, Dr. biol. hum., Senior Scientist
+49 511 532 4320 | Borst.Eva@MH-Hannover.de
Harmening, Sarah, M.Sc. Biochemistry, PhD student
+49 511 532 4321 | Harmening.Sarah@mh-hannover.de
Siemes, Anna Rebecca, M.Sc. Biomedical Sciences, PhD student
+49 511 532 4321 | Siemes.Anna@mh-hannover.de
Szymanska-De Wijs, Katarzyna, M.Sc. Biotechnology, PhD student
+49 511 532 6493 | Szymanska-DeWijs.Katarzyna@mh-hannover.de
Wagner, Karen, Research assistant
+49 511 532 4321 | Wagner.Karen@MH-Hannover.de
Alumni of the Group
Dr. rer. nat. Eleonora Naimo
Dr. Martina Dezeljin, (Institute Ruder Boskovic, CRO/Zagreb)
Ivana Kutle – Dr.rer.nat. (Helmholtz-Institut for Infection Research; GER/Brunswick)
Sebastian Neuber – M.Sc. Biochemistry, Dr.rer.nat. (Metanomics, GER/Berlin)
Shahab Nahrevanian, Dr.rer.nat.
Nadine Thiel – M.Sc. Biochemistry, Dr.rer.nat., (DSMZ GmbH Braunschweig, GER/Brunswick)
Adriana Tomic – Dipl. Biol., PhD, Postdoc "promotion winner", (Stanford University, CA)
Daniel Malouli, Dipl.Biochem., Dr. rer. nat. (Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, USA)
Endrit Elbasani – Dipl. Biol., PhD, Postdoc, (University of Helsinki, FI)
Ildar Gabaev – Dipl. Biol., PhD, Postdoc, (University Cambridge, UK)
Kirsten Keyser – Dr.rer.nat., Postdoc (Sysmex Inostics, GER/HAM)
Andreas Busche - Dr.rer.nat., (Biotech Burgwedel MSD, GER)
Mandy Glaß – Dipl.Biochem., Dr. rer. nat., (University of Western Scotland, GL)
Penelope Kay-Jackson - PhD, Postdoc (Institute of Virology, GER/Hannover)
Jennifer Kleine-Albers - PhD student, Dr.rer.nat. (Mylan Healthcare, GER/Hannover)
Anja Marquardt - Dipl. Biol., PhD student, Dr.rer.nat. (Octapharma, GER/Springe)
Nadine Müther - Dipl. Biol., PhD student, Dr.rer.nat., (Novartis, GER/Marburg)
Christoph Peter - Dipl. Biol., PhD student, Dr.rer.nat.
Corinna Benkartek - Dipl. Biol., PhD student, Dr.rer.nat., (Xcenda GmbH, GER/Hanover)
Sarah Sengstake - Dipl. Biol., PhD student, Dr.rer.nat., (Institute of Tropical Medicine Antwerpen, BEL)
Role of cytomegalovirus UL25 protein family members for cell-to-cell spread in persisting infection
Visualization of herpesvirus infections and immune response as well as their modulation
- Herpesviral assembly
(in collaboration with Profs. Grünewald, Krey and Sodeik)
- Development of novel anti-HCMV drugs with new modes of action
(Collaboration with Prof. Dr. Wolfram Brune, Heinrich-Pette-Institute Hamburg and PD Dr. Zsolt Ruzsics, University of Freiburg)
- Mechanisms of human cytomegalovirus capsid maturation
PI: Dr. Eva Maria Borst
- Role of NKG2D ligands for activation of the human cytomegalovirus specific immune response
(DFG Research Group FOR 2830) Advanced Concepts in Cellular Immune Control of Cytomegalovirus)
(Collaboration with Prof. Christine Falk, Institute of Transplant Immunology)
Publications in peer-reviewed journals, Reviews, Book chapters, Comments etc.
1. Hammer Q, Rückert T, Borst EM, Dunst J, Haubner A, Durek P, Heinrich F, Gasparoni G, Babic M, Tomic A, Pietra G, Nienen M, Blau IW, Hofmann J, Na IK, Prinz I, Koenecke C, Hemmati P, Babel N, Arnold R, Walter J, Thurley K, Mashreghi MF, Messerle M, Romagnani C. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells.
Nat Immunol. 2018, 19:453-463.
2. Kutle I, Sengstake S, Templin C, Glaß M, Kubsch T, Keyser KA, Binz A, Bauerfeind R, Sodeik B, Čičin-Šain L, Dezeljin M, Messerle M. The M25 gene products are critical for the cytopathic effect of mouse cytomegalovirus.
Scientific Reports 2017, 7:e15588.
3. Neuber S, Wagner K, Goldner T, Lischka P, Steinbrueck L, Messerle M, Borst EM. Mutual interplay between the human cytomegalovirus terminase subunits pUL51, pUL56, and pUL89 promotes terminase complex formation.
J Virol. 2017, 9: e02384-16.
4. Borst EM, Bauerfeind R, Binz A, Stephan TM, Neuber S, Wagner K, Steinbrück L, Sodeik B, Lenac Roviš T, Jonjić S, Messerle M. The essential human cytomegalovirus proteins pUL77 and pUL93 are structural components necessary for viral genome encapsidation
J Virol. 2016, 90:5860-75.
5. Thiel N, Keyser KA, Lemmermann NA, Oduro JD, Wagner K, Elsner C, Halenius A, Lenac Roviš T, Brinkmann MM, Jonjić S, Cicin-Sain L, Messerle M. The mouse cytomegalovirus gene m42 targets surface expression of the protein tyrosine phosphatase CD45 in infected macrophages.
PLoS Pathog. 2016, 12:e1006057.
6. Tomić A, Varanasi PR, Golemac M, Malić S, Riese P, Borst EM, Mischak-Weissinger E, Guzmán CA, Krmpotić A, Jonjić S, Messerle M. Activation of innate and adaptive immunity by a recombinant human cytomegalovirus strain expressing an NKG2D ligand.
PLoS Pathog. 2016, 12:e1006015.
7. Halle S, Keyser KA, Stahl FR, Busche A, Marquardt A, Zheng X, Galla M, Heissmeyer V, Heller K, Boelter J, Wagner K, Bischoff Y, Martens R, Braun A, Werth K, Uvarovskii A, Kempf H, Meyer-Hermann M, Arens R, Kremer M, Sutter G, Messerle M, Förster R. In vivo killing capacity of cytotoxic T cells is limited and involves dynamic interactions and T cell cooperativity.
Immunity 2016, 44:233-45.
8. Borst EM, Kleine-Albers J, Gabaev I, Babic M, Wagner K, Binz A, Degenhardt I, Kalesse M, Jonjic S, Bauerfeind R, Messerle M. The human cytomegalovirus UL51 protein is essential for viral genome cleavage-packaging and interacts with the terminase subunits pUL56 and pUL89.
J Virol. 2013, 87:1720-32.
9. Busche A, Jirmo AC, Welten SP, Zischke J, Noack J, Constabel H, Gatzke AK, Keyser KA, Arens R, Behrens GM, Messerle M. Priming of CD8+ T cells against cytomegalovirus-encoded antigens is dominated by cross-presentation.
J Immunol. 2013, 190:2767-77.
10. Trsan T, Busche A, Abram M, Wensveen FM, Lemmermann NA, Arapovic M, Babic M, Tomic A, Golemac M, Brinkmann MM, Jäger W, Oxenius A, Polic B, Krmpotic A, Messerle M, Jonjic S. Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ.
Proc Natl Acad Sci USA 2013, 110:16550-5.
11. Slavuljica I, Busche A, Babić M, Mitrović M, Gašparović I, Cekinović D, Markova Car E, Pernjak Pugel E, Ciković A, Lisnić VJ, Britt WJ, Koszinowski U, Messerle M, Krmpotić A, Jonjić S. Recombinant mouse cytomegalovirus expressing a ligand for the NKG2D receptor is attenuated and has improved vaccine properties.
J Clin Invest. 2010, 120:4532-45.
12. Glaß, M., Busche, A., Wagner, K., Messerle, M., Borst, E.M. Conditional and reversible disruption of essential herpesvirus proteins.
Nature Methods 2009, 6:577-9.
13. Borst, E.M., 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.
14. 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 USA 1997, 94:14759-63.
Complete Publication list: