[993] Emerging viruses

 

My research interests are the laboratory-based risk assessment of novel and emerging viruses. This includes the development of epithelial cell culture models from reservoir hosts such as bats and rodents, the assessment of viral diversity and virus discovery in both humans and animals and the epidemiology of novel emerging viruses e.g. corona- and arboviruses. Further research interests in the field of clinical virology include imported virus infections from returning travellers and infections and vaccine response in immunocompromised hosts.

 

1. Development of innovative cell culture models of reservoir hosts

The research on zoonotic viruses suffers from a lack of suitable in vitro models. The value of conventional laboratory systems such as mouse models or tumour cell lines is low since the evolutionary conserved pathogen-host interaction of zoonotic viruses in their natural reservoir is not reflected. Furthermore, the most interesting reservoir host species, e.g. tropical bats and rodents are not suitable as animal models as they cannot be held or bred in captivity. Therefore, permanent cell cultures derived from natural reservoir host can serve as a valid surrogate. In the recent years, an algorithm was developed for the generation of permanent cell lines from wild caught small mammals across a large range of geographical areas. A focus of this process lies in the cryo-conservation of tissues in order to isolate primary epithelial cell lines after shipping from tropical and remote areas. Immortalization was conducted by lentiviral transfer of the large T-Antigen of SV40; further aspects included characterization of the cell type of origin and exclusion of contamination. By this method, more than 70 epithelial cell lines have been generated from 18 different small mammals as well as a two livestock species. A subset of these cell lines were evaluated as model systems for replication of more than 20 viruses such as arboviruses, hantaviruses and coronavirus. Furthermore, virus isolation trials using reservoir-derived cell lines may provide important benefits for reservoir-restricted viruses which could not be isolated in most instances on conventional cell lines such as Vero cells. The cells lines generated can be used under standard cell culture conditions and resulted in a number of national and international collaboration projects in which these novel cell culture models are used for a variety of aspects on virus-host interaction studies

 

2. Assessment of viral diversity and virus discovery

In order to perform an immediate risk assessment in case a novel human virus emerges, a thorough understanding of virus diversity is an important prerequisite. Therefore, a focus of my research activities is the “OneHealth” approach, including interdisciplinary work with veterinarians, microbiologists and human medical doctors and the analysis of wildlife, livestock and human samples by next-generation sequencing, newly developed serological methods and generic PCR amplification methods. Furthermore the combination of virus discovery methods along with classical virological methods based on phenotypic cell culture characterization provides a benefit to sequence-only based virus discovery findings that can never fully elucidate a virus’ biological properties.

 

3. Epidemiology of novel emerging viruses

The mainstay in the work on emerging viruses is reflected in the term of “pandemic preparedness”. This includes all diagnostic aspects of novel viruses, development of biobanks and generic sampling protocols and set-up of clinical studies in an international context of both high- and low resource countries. Previous work in this area involved screening and detection of novel and (re-emerging) viruses, such as screening returning Hajj pilgrims from Saudi Arabia for assessment of MERS-CoV and other respiratory viruses, the description of the viral diversity by next-generation sequencing in children with acute upper respiratory tract infection in Germany, epidemiology of respiratory viruses in children with fever without source in Ghana, epidemiology of encephalitis 

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