Study of cellular and molecular mechanisms of Nipah virus pathogenesis

• Applicant: Dr. Christine Pohl
• Subject Area: Virology
• Term: from 2008 to 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 99387372

Nipah virus (NiV), a recently emerged paramyxovirus, causes encephalitis in humans with mortality rates of 40-70 %. It is the most severe zoonose recently emerged and has provoked serious medical and economical problems in East Asia. Neither efficient treatment nor a vaccine is currently available and it is therefore important to understand the pathogenesis of this emergent infection. This project thus aims to analyse the cellular and molecular basis of NiV pathogenesis and requires the use of a high security BSL-4 laboratory. First, NiV tropism will be studied in vitro in order to identify cell types involved in virus propagation in the host organism early after infection. Primary human cells will be examined for their ability to support virus replication and to produce cytokines. Also, the role of non-structural viral proteins, known to interfere with the host’s immune response, will be analysed in human cells using recombinant viruses lacking one of these proteins. Second, the hamster animal model will be used to reveal the pathways exploited by the virus in the organism, particularly for neuroinvasion. Hamsters, which develop a disease closely resembling that in humans, will be infected with a recombinant NiV that expresses green-fluorescent protein permitting rapid detection of infected cells with high sensitivity. The pathogenicity of recombinant viruses lacking non-structural NiV genes will be equally analysed in vivo. These studies will provide a basic insight in NiV pathogenesis and help develop novel immunotherapeutic strategies against this emerging disease.

• DFG Programme: Research Fellowships
• International Connection: France
• Host: Professorin Dr. Branka Horvat