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Chracterization of the molecular features of the pestivirus Erns protein with regard to its function as structural component of the virion and virulence factor
Project
Project code: FLI-IfI-08-Ri-0473
Contract period: 01.06.2016
- 31.05.2018
Purpose of research: Basic research
The Erns protein of pestiviruses represents a specifically interesting viral protein since it combines the role of a structural surface protein with functions in repression of the type 1 interferon response, establishment of persistent infection and virulence in the natural host with the latter three features linked to the RNase activity of this protein. The mechanisms underlying both functions of the protein are not known in detail and will be investigated in the planned studies. Major questions in context with the function as a structural protein concern the role of Erns in virion assembly and budding and identification of the structure responsible for sorting of the protein into the virus particle. A special focus of the work will be on the importance of the unusual Erns membrane anchor with its conserved amino acid motifs for these processes. The virulence factor function of Erns is so far regarded to depend on its intrinsic RNase activity, its dimerization and its partial secretion form the host cell. The planned work aims at elucidation of the biochemical and cell biological basis of these features of Erns. The results of this work will contribute to understanding general aspects of pestivirus biology and the interaction of these viruses with the immune system of their hosts.
One of the unusual properties of the Erns glycoprotein concerns its membrane anchor consisting of a long amphipathic helix that is also important for processing, intracellular retention and dimer formation of the protein and contains several remarkable sequence motifs. Alteration of amino acids in these motifs can lead to significant changes of Erns processing, secretion and dimerization. When introduced into the viral genome, some of these mutations cannot be tolerated and lead to immediate reversion or pseudoreversion or prevent the generation of infectious virus particles. A pseudorevertant gen
erated within animals infected with an attenuated mutant defective in Erns dimerization was shown to have regenerated the ability to form Erns dimers and to partially restore virulence. The underlying mechanisms are further analyzed in the next funding period. Tucakov AK, Yavuz S, Schürmann EM, Mischler M, Klingebeil A, and Meyers G 2018. Restoration of glycoprotein Erns dimerization via pseudoreversion partially restores virulence of classical swine fever virus. J Gen Virol. 99:86-96. doi: 10.1099/jgv.0.000990
Section overview
Subjects
- Animal health
- Biotechnology
