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Research Group PD Dr. rer. nat. Barbara Adler

HCMV glycoprotein complexes controlling virus entry and virus-induced immune responses

Areas of investigation

Virus entry depends on specific interactions of glycoproteins on the surface of virus particles and cell surface proteins. Complex viruses like herpesviruses do not only express one receptor binding protein which mediates receptor recognition and entry, but at least five different glycoproteins which in concert promote attachment to cell surfaces, recognition of specific entry receptors, stimulation of co-receptors, and fusion of viral and host cell membranes. Those glycoproteins which promote recognition of entry receptors and membrane fusion are the essential “keys” for virus infection.
My laboratory is interested in the interaction of cytomegaloviruses and their host cells with a focus on viral glycoprotein complexes promoting virus entry and the importance of these glycoprotein complexes in cytomegalovirus vector design.

1. Basic research on interactions of viral glycoproteins with host cell receptors

We are interested in human cytomegalovirus (HCMV) and as a model system in murine cytomegalovirus (MCMV). HCMV is spread worldwide and shows a seroprevalence between 40 and up to 90 %. Infections of healthy humans with HCMV usually are asymptomatic, but they can cause life-threatening diseases in immune-deficient patients like transplant, cancer or AIDS patients. Importantly, HCMV infections during pregnancy are the most frequent congenital virus infections leading to severe neurological defects like microcephaly.
The envelope glycoproteins in focus of our research are the HCMV gH/gL glycoprotein complexes, gH/gL/gO and gH/gL/pUL(128-131A), which determine the cell tropism of HCMV. The cellular receptors targeted by these complexes are not known.
Our major tool to study the role of gH/gL complexes in CMV infection are virus genomes cloned by BAC (bacterial artificial chromosome) - technology, a technique which involves cloning of the more than 200.000 bp long CMV genomes in bacterial vectors and subsequent mutagenesis in E.coli:

Using BAC-technology we can for example delete constituents of the gH/gL complexes and study their role in entry:

or overexpress glycoproteins to study their intracellular localization:

For HCMV, we study which glycoproteins of the gH/gL complexes are essential for recognition of specific host cell receptors and how infection in cell culture is changed if a constituent of the gH/gL complexes is missing or mutated. Additionally, we search for host cell receptors recognized by these complexes.
We complement our basic findings in cell culture with studies on the role of the homologous gH/gL complexes of MCMV in the infection of the mouse. This allows us to evaluate the role of gH/gL complexes in the infected host, a prerequisite for the design of antiviral therapies targeting gH/gL complexes.

2. Design of viral vectors for immune therapy of infectious diseases and tumors

gH/gL complex action is not restricted to promotion of virus entry, but also plays a role in modulation of virus-induced immune responses. In the context of application of CMV genomes as vaccine vectors for immune therapy of chronic infectious diseases and tumors, we study the immune response elicited by MCMV vectors with modified gH/gL complexes.

Current Group Members

Barbara Adler, PhD, PD, group leader
Email: adler_b(at)mvp.uni-muenchen.de

Marwa Eletreby, PhD student
Email: eletreby@mvp.uni-muenchen.de
Phone +49 89-2180-72889

Josipa Jerak, Master of Science
Email: jerak(at)mvp.uni-muenchen.de
Phone +49 89-2180-72889

Former lab members

Regina Bichler (Bachelor student)
Ilija Brizic (visiting PhD student)
Heike Hofmann (Technician)
Laura Jochem (Bachelor student)
Marisa Kurz (Bachelor Student)
Adrian Prager (Technician)
Sabrina Schuller (Bachelor student)
Laura Scrivano (PhD student and postdoc)
Jasmina Esterlechner (Master student)
Yiquan Wu (PhD student)
Thomas Deiler (bachelor student)


Recent key publications
Hagen C., Dent K.C., Zeev-Ben-Mordehai T., Grange M., Bosse J.B., Whittle C., Klupp B.G., Siebert C.A., Vasishtan D., Bäuerlein F.J., Cheleski J., Werner S., Guttmann P., Rehbein S., Henzler K., Demmerle J., Adler B., Koszinowski U., Schermelleh L., Schneider G., Enquist L.W., Plitzko J.M., Mettenleiter T.C., Grünewald K. (2015) Structural Basis of Vesicle Formation at the Inner Nuclear Membrane. Cell 163(7),1692-701.
Lemmermann, N.A., Krmpotic, A., Podlech, J., Brizic, I., Prager ,A., Adler, H., Karbach, A., Wu, Y., Jonjic, S., Reddehase, M.J., and Adler, B. (2015) Non-redundant and redundant roles of Cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread. PLoS Pathog 11(2):e1004640
Wagner, F., Brizic, I., Prager, A., Trsan, T., Arapovic, M., Lemmermann, N.A.W., Podlech, J., Reddehase, M.J., Lemnitzer, F., Bosse, J-B., Gimpfl, M., Marcinowski, L., MacDonald, M., Adler, H., Koszinowski, U.H. and Adler, B. (2013) The Viral Chemokine MCK-2 of Murine Cytomegalovirus Promotes Infection as Part of a gH/gL/MCK-2 Complex. PLoS Pathog 9(7): e1003493
Jordan, S., Krause, J., Prager, A., Mitrovic, M., Jonjic, S., Koszinoswki, U.H., and Adler, B. (2011) Virus progeny of Murine Cytomegalovirus Bacterial Artificial Chromosome pSM3fr show reduced growth in Salivary Glands due to fixed mutation of MCK-2. J.Virol. 85, 10346-10353
Scrivano, L., Sinzger C., Nitschko, H., Koszinowski, U.H. and Adler, B. (2011) HCMV spread and cell tropism are determined by distinct virus populations. PLoS Pathog 7(1): e10011256


PD Dr. Barbara Adler
Max von Pettenkofer Institute, Virology
National Reference Center for Retroviruses
Faculty of Medicine
LMU München
Feodor-Lynen-Straße 25
81377 Munich, Germany
Tel.: 089-2180-76863 / Labor -76850
Email: adler_b(at)mvp.uni-muenchen.de