Center for Molecular Medicine Cologne

Olaf Utermöhlen - assoc. RG

Pathogenicity of Zika Virus strains in various host cell types

Abstract

The emergence of Zika virus (ZIKV) in Central America in 2015 coincided with a surge in the incidence of microcephaly. A growing body of epidemiological and experimental evidence strengthens the assumption that prenatal ZIKV infection causes microcephaly.
This project aims at characterizing the pathogenicity of ZIKV in neurologically relevant cells. Furthermore, it is still an open question, whether Zika isolates from Africa versus Asia/South America differ in their pathogenicity.
We have a collection of ZIKV strains from recent outbreaks in Polynesia and Central America and from endemic areas in Africa. Additionally, we have different cell cultures systems for neurologically relevant cell types. With these experimental systems, we will elucidate whether specific ZIKV strains differ in their pathogenicity and we will characterize underlying molecular mechanisms.
This project will provide a contribution to understanding the impact of ZIKV infection on brain development, which is required for prophylactic and therapeutic approaches against the sequelae of the global ZIKV epidemics.

Clinical/medical relevance and sustainability in disease understanding

Accumulating epidemiological evidence and data from in vitro models of human brain development suggest that prenatal Zika virus infection causes severe fetal brain malformations, including microcephaly. Virological aspects as well as the cellular and molecular mechanisms of the impact of ZIKV infection on brain development need to be characterized in order to assess target-oriented prophylactic and/or therapeutic approaches to prevent ZIKV-induced fetal malformations in the future.

Herb, M., Gluschko, A., Wiegmann, K., Farid, A., Wolf, A., Utermohlen, O., Krut, O., Kronke, M., and Schramm, M. (2019). Mitochondrial reactive oxygen species enable proinflammatory signaling through disulfide linkage of NEMO. Sci Signal 12.

Sanchez-Ruiz, M., Polakos, N.K., Blau, T., Utermohlen, O., Brunn, A., Montesinos-Rongen, M., Hunig, T., and Deckert, M. (2019). TLR signals license CD8 T cells to destroy oligodendrocytes expressing an antigen shared with a Listeria pathogen. Eur J Immunol 49, 413-27.

Utermohlen, O., Jakobshagen, K., Blissenbach, B., Wiegmann, K., Merz, T., Hefti, J.P., and Kronke, M. (2019). Emergence of AnnexinVpos CD31neg CD42blow/neg extracellular vesicles in plasma of humans at extreme altitude. PLoS One 14, e0220133.

von Bargen, K., Scraba, M., Kramer, I., Ketterer, M., Nehls, C., Krokowski, S., Repnik, U., Wittlich, M., Maaser, A., Zapka, P., Bunge, M., Schlesinger, M., Huth, G., Klees, A., Hansen, P., Jeschke, A., Bendas, G., Utermohlen, O., Griffiths, G., Gutsmann, T., Wohlmann, J., and Haas, A. (2019). Virulence-associated protein A from Rhodococcus equi is an intercompartmental pH-neutralising virulence factor. Cell Microbiol 21, e12958.

Gluschko A, Herb M, Wiegmann K, Krut O, Neiss WF, Utermohlen O, Kronke M, and Schramm M (2018). The beta2 Integrin Mac-1 Induces Protective LC3-Associated Phagocytosis of Listeria monocytogenes. Cell Host Microbe 23, 324-337 e325.

von Bargen K, Scraba M, Kramer I, Ketterer M, Nehls C, Krokowski S, Repnik U, Wittlich M, Maaser A, Zapka P, Bunge M, Schlesinger M, Huth G, Klees A, Hansen P, Jeschke A, Bendas G, Utermohlen O, Griffiths G, Gutsmann T, Wohlmann J, and Haas A (2018). VapA from Rhodococcus equi is an inter-compartmental pH-neutralising virulence factor. Cell Microbiol 10.1111/cmi.12958, e12958.

Brunn A, Mihelcic M, Carstov M, Feind L, Wieser EC, Schmidt J, Utermohlen O, and Deckert M (2017). Toll-Like Receptor 2, Toll-Like Receptor 4, Myeloid Differentiation Response Gene 88, and Toll-IL-1 Receptor Domain-Containing Adaptor-Inducing Interferon-gamma (TRIF) Selectively Regulate Susceptibility of P0106-125-Induced Murine Experimental Autoimmune Neuritis. Am J Pathol 187, 42-54.

Gabriel E, Ramani A, Karow U, Gottardo M, Natarajan K, Gooi LM, Goranci-Buzhala G, Krut O, Peters F, Nikolic M, Kuivanen S, Korhonen E, Smura T, Vapalahti O, Papantonis A, Schmidt-Chanasit J, Riparbelli M, Callaini G, Kronke M, Utermohlen O, and Gopalakrishnan J (2017). Recent Zika Virus Isolates Induce Premature Differentiation of Neural Progenitors in Human Brain Organoids. Cell Stem Cell 20, 397-406 e5.

Hosel M, Huber A, Bohlen S, Lucifora J, Ronzitti G, Puzzo F, Boisgerault F, Hacker UT, Kwanten WJ, Kloting N, Bluher M, Gluschko A, Schramm M, Utermohlen O, Bloch W, Mingozzi F, Krut O, and Buning H (2017). Autophagy determines efficiency of liver-directed gene therapy with adeno-associated viral vectors. Hepatology10.1002/hep.29176.

Wennhold K, Thelen M, Schlosser HA, Haustein N, Reuter S, Garcia-Marquez M, Lechner A, Kobold S, Rataj F, Utermohlen O, Chakupurakal G, Theurich S, Hallek M, Abken H, Shimabukuro-Vornhagen A, and von Bergwelt-Baildon M (2017). Using Antigen-Specific B Cells to Combine Antibody and T Cell-Based Cancer Immunotherapy. Cancer Immunol Res 5, 730-43.

Former Funding Period 01/2017 - 12/2019

Information from this funding period will not be updated anymore. New research related information is available here.

Prof. Dr. Olaf Utermöhlen CMMC Cologne
Prof. Dr. Olaf Utermöhlen

Inst. for Med. Microbiology, Immunology and Hygiene

Executive Board Member

+49 221 478 32023

+49 221 478 32002

Inst. for Med. Microbiology, Immunology and Hygiene

Goldenfelsstr. 19 – 21

50935 Cologne

http://immih.uk-koeln.de/forschung/ag-utermoehlen

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Curriculum Vitae (CV)

Publications - Olaf Utermöhlen

Link to PubMed