Viral evasion of innate and adaptive immune cells and ‘inbetweeners’

Abstract:

Evasion of innate and adaptive immune responses is a common feature of tumors and chronic viral infections. An active interference with the presentation of antigenic peptides by MHC class-I and -II molecules is a strategy to prevent altered-self/non-self recognition by CD8 and CD4 T cells. Downregulation and upregulation of ligands of activatory and inhibitory receptors, respectively, is a strategy to silence natural killer (NK) cells. At the innate-adaptive immunity interface, downregulation of self and foreign lipid-presenting CD1d molecules is a means to evade invariant NKT (iNKT) cells, ‘inbetweeners’ acting as instant regulators of classically innate and adaptive immune responses.

The project aims at identifying mechanisms by which cytomegalovirus (CMV) genes modulate the immune response as well as mechanisms by which the host can regulate the expression of these CMV immune modulators. Learning how the host eventually manages to keep a chronic virus in check irrespective of its immune evasion strategies may reveal concepts of how to improve immune surveillance also of malignant cells.

Principal investigators:

PD Dr. rer. physiol. et med. habil. Niels A. Lemmermann
Institut für Virologie
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Obere Zahlbacher Straße 67, 55131 Mainz
Phone: +49 (0)6131 17-9184
E-mail: lemmermann@uni-mainz.de
Web: https://www.blogs.uni-mainz.de/juggle/dr-niels-lemmermann/
http://www.unimedizin-mainz.de/virologie/research/research-groups/ag-lemmermann-reddehase.html

Univ.-Prof. Dr. rer. nat. Matthias J. Reddehase
Institut für Virologie
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Obere Zahlbacher Straße 67, 55131 Mainz
Phone: +49 (0)6131 17-9230
E-mail: matthias.reddehase@uni-mainz.de
Web: http://www.unimedizin-mainz.de/index.php?id=13713

Doctoral candidates:

Sara Becker

Julia Schmiedeke

 

Project-related publications:

Reddehase MJ (2016) Mutual interference between cytomegalovirus and reconstitution of protective immunity after hematopoietic cell transplantation. Front Immunol 7:294

Fink A, Blaum F, Babic Cac M, Ebert S, Lemmermann NA, Reddehase MJ (2015) An endocytic YXXΦ (YRRF) cargo sorting motif in the cytoplasmic tail of murine cytomegalovirus AP2 'adapter adapter' protein m04/gp34 antagonizes virus evasion of natural killer cells. Med Microbiol Immunol 204:383-394

Lemmermann NA, Krmpotic A, Podlech J, Brizic I, Prager A, Adler H, Karbach A, Wu Y, Jonjic S, Reddehase MJ*, Adler B* (2015) Non-redundant and redundant roles of cytomegalovirus gH/gL complexes in host organ entry and intra-tissue spread. PLoS Pathog 11:e1004640

Thomas S, Klobuch S, Podlech J, Plachter B, Hoffmann P, Renzaho A, Theobald M, Reddehase MJ*, Herr W*, Lemmermann NA* (2015) Evaluating human T-cell therapy of cytomegalovirus organ disease in HLA-transgenic mice. PLoS Pathog 11:e1005049

Ebert, S, Becker M, Lemmermann NA, Büttner JK, Michel A, Taube C, Podlech J, Böhm V, Freitag K, Thomas D, Holtappels R*, Reddehase MJ*, Stassen M* (2014) Mast cells expedite control of pulmonary murine cytomegalovirus infection by enhancing the recruitment of protective CD8 T cells to the lungs. PLoS Pathog 10: e1004100

Fink, A, Renzaho A, Reddehase MJ*, Lemmermann NA* (2013) The p36 isoform of murine cytomegalovirus m152 protein suffices for mediating innate and adaptive immune evasion. Viruses 5: 3171-3191

Lemmermann NA, Fink A, Podlech J, Ebert S, Wilhelmi V, Böhm V, Holtappels R, Reddehase MJ (2012) Murine cytomegalovirus immune evasion proteins operative in the MHC class I pathway of antigen processing and presentation: state of knowledge, revisions, and questions. Med Microbiol Immunol 201:497-512

Wilhelmi V, Simon CO, Podlech J, Böhm V, Däubner T, Emde S, Strand D, Renzaho A, Lemmermann NA, Seckert CK, Reddehase MJ*, Grzimek NK (2008) Transactivation of cellular genes involved in nucleotide metabolism by the regulatory IE1 protein of murine cytomegalovirus is not critical for viral replicative fitness in quiescent cells and host tissues. J Virol 82:9900-9916

Holtappels R, Podlech J, Pahl-Seibert MF, Jülch M, Thomas D, Simon CO, Wagner M, Reddehase MJ (2004) Cytomegalovirus misleads its host by priming of CD8 T cells specific for an epitope not presented in infected tissues. J Exp Med 199:131-136

Reddehase MJ (2002) Antigens and immunoevasins: opponents in cytomegalovirus immune surveillance. Nat Rev Immunol 2: 831-844