The exploitation of natural resources, global travel, climate change and other factors result in the constant introduction of new viruses (emerging viruses) into the human population. These viruses are frequently transmitted from animals to humans and cause severe disease, since they are not adapted to the human host. Non-human primates (NHP) can play an important role in the zoonotic transmission of emerging viruses and severe as important models, which allow analysis of viral pathogenesis and testing of therapeutics and vaccines.
Lassa virus is a highly pathogenic arenavirus that is transmitted from rodents to humans and is responsible for several thousand deaths each year in Africa. The lymphocytic choriomeningitis virus (LCMV) is also transmitted from rodents to humans. In contrast to Lassa virus, LCMV is circulating globally and infection is usually not associated with severe disease. However, there is evidence that LCMV can be a threat to pregnant women and their unborn children. Moreover, lethal infection with LCMV and the closely related Dandenong have been observed in immunosuppressed patients. Finally, LCMV has caused outbreaks of lethal hepatitis in marmoset colonies. LCMV isolates exhibit a substantial sequence diversity. However, it is largely unclear whether certain LCMV variants constitute a particular threat to NHP and humans and this question is addressed by Dr. Markus Hoffmann.
The Ebola virus causes a severe and frequently fatal disease in NHP and humans. Ebola-outbreaks have decimated chimpanzee and gorilla colonies, and the Ebola epidemic in Western Africa during 2014-2016 claimed more than 10.000 human lives. The development of countermeasures critically depends on NHP, since these animals constitute the most important animal model for Ebola virus infection of humans. Dr. Heike Hofmann-Winkler and Dr. Markus Hoffmann investigate how Ebola virus enters human and NHP cells and how the virus counters the interferon response of the host. For this, we use surrogate systems, which allow analysis of Ebola virus spread without using infectious virus.
Another focus of our work is on Middle East Respiratory Syndrome-Coronavirus (MERS-CoV). MERS-CoV is transmitted from dromedary camels to humans and constitutes a severe health threat in the Middle East. Moreover, air travel can result in MERS outbreaks in any country, with hospitals being particularly vulnerable. The cellular protease TMPRSS2 can activate the MERS-CoV. Therefore, we are investigating whether the efficiency of TMPRSS2 usage is a predictor of transmissibility and pandemic potential. Moreover, we are analyzing whether TMPRSS2 inhibitors can be used for therapy of MERS. For this, we will implement a marmoset-based model, once the BSL3 animal unit at DPZ is operational. This is currently the only animal model which mirrors fatal human infections and does not require MERS-CoV adaptation to the host or genetic modification of the host.
Kleine-Weber H., M.T. Elzayat , L. Wang, B.S. Graham, M.A. Müller, C. Drosten, S. Pöhlmann and M. Hoffmann. Mutations in the spike protein of MERS-CoV transmitted in Korea increase resistance towards antibody-mediated neutralization. J Virol In press
Hoffmann M., I. Nehlmeier, C. Brinkmann, V. Krähling, L. Behner, A.S. Moldenhauer, N. Krüger, J. Nehls, M. Schindler, T. Hoenen, A. Maisner, S. Becker and S. Pöhlmann. Tetherin inhibits Nipah virus but not Ebola virus replication in fruit bat cells. J Virol In press
Guo Y., I. Nehlmeier, E. Poole, C. Sakonsinsiri, N. Hondow, A. Brown, Q. Li, S. Li, J. Whitworth, Z. Li, A. Yu, R. Brydson, W.B. Turnbull, S. Pöhlmann and D. Zhou. Dissecting Multivalent Lectin-Carbohydrate Recognition Using Polyvalent Multifunctional Glycan-Quantum Dots. J Am Chem Soc. 2017 doi: 10.1021/jacs.7b05104.
Hoffmann M., L. Crone, E. Dietzel, J. Paijo, M. González-Hernández, I. Nehlmeier, U. Kalinke, S. Becker and S. Pöhlmann. A Polymorphism within the Internal Fusion Loop of the Ebola Virus Glycoprotein Modulates Host Cell Entry. J. Virol. 2017 13;91(9).
Brinkmann C., I. Nehlmeier, K. Walendy-Gnirß, J. Nehls, M. González Hernández, M. Hoffmann, X. Qiu, A. Takada, M. Schindler and S. Pöhlmann. The Tetherin Antagonism of the Ebola Virus Glycoprotein Requires an Intact Receptor-Binding Domain and Can Be Blocked by GP1-Specific Antibodies. J. Virol. 2016 90(24):11075-11086. IF:4.7.
Hofmann-Winkler H., K. Gnirß, F. Wrensch and S. Pöhlmann. Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976. J Infect Dis. 2015 212 S172-80.
More information on the MERS and Ebola research of the working group "Emerging viruses" can be found in the following issues of the magazine "DPZ aktuell" (please click on the picture to read the articles).