Professor of Medical and Pharmaceutical Biotechnology
Department of Life Sciences
University of Applied Sciences Krems
Campus Krems, Building G, Room 3.20
3500 Krems an der Donau
Phone: +43 (2732) 802-883
FAX: +43 (2732) 802-4
Virus-host interactions, innate immune response, non-coding RNAs, systems biology
Virus-host interactions during adenovirus infection
We are interested in the interplay between human adenoviruses and their host cells. Adenoviruses elicit an innate immune response, yet are able to dampen this response with the help of virus-encoded non-coding RNAs. These non-coding RNAs are processed into shorter fragments of which the larger ones are able to block protein kinase R (PKR). The shorter ones function as microRNAs (miRNAs) and are capable of downregulating the expression of certain cellular genes. Preliminary data generated by us point towards a potential role of these miRNAs in the inhibition of cytokine-mediated proinflammatory responses in infected cells and possibly in surrounding, uninfected, cells via a virus-independent transduction mechanism.
This effect may not only have an impact during acute infection but also during virus latency in which the viruses are able to persist in certain cell types such as T- and B-lymphocytes for prolonged times. Besides, we are interested in the identification cellular genes that are essential for viral replication and in the generation of molecular tools that might be exploited in the inhibition of adenovirus replication.
Bellutti, F., Kauer, M., Kneidinger, D., Lion, T., Klein, R. 2015. RNA-Seq- and microarray-based identification of RISC-associated adenoviral miRNAs, a subset of their direct targets, and global changes in the cellular targetome. J. Virol. 3: 1608-27.
Ibrišimović, M., Lion, T., Klein, R. 2013. Combinatorial targeting of 2 different steps in adenoviral DNA replication by herpes simplex virus thymidine kinase and artificial microRNA expression for the inhibition of virus multiplication in the presence of ganciclovir. BMC Biotechnol. 3 Jul 3; 13(1): 54.
Ibrišimović, M., Kneidinger, D., Lion, T., Klein, R. 2013. An adenoviral vector-based expression and delivery system for the inhibition of wild-type adenovirus replication by artificial microRNAs. Antiviral Res. 97: 10-23.
Kneidinger, D., Ibrišimović, M., Lion, T., Klein, R. 2012. Inhibition of adenovirus multiplication by short interfering RNAs directly or indirectly targeting the viral DNA replication machinery. Antiviral Res. 94: 195-207.
Ibrišimović, M., Nagl, U., Kneidinger, D., Rauch, M., Lion, T., and Klein, R. Targeted expression of herpes simplex virus thymidine kinase in adenovirus-infected cells reduces virus titers upon treatment with ganciclovir in vitro. J. Gene Med. 14: 3-19.