Basolateral transport of the Nipah virus glycoproteins in polarized epithelial cells
|Projektleiter/in||Prof. Dr. Andrea Maisner|
|Weitere Bearbeiter/innen||Sandra Diederich, Stephanie Erbar|
Epithelial cells serve as a primary protective barrier against microorganisms and possess two strictly separated membrane domains. The apical side normally faces the lumen whereas the basolateral side is in contact with underlying tissues and the blood system. Due to polarized protein and lipid sorting in these cells, virus-encoded proteins are often expressed in a polarized fashion. As a consequence, virus spread and release from epithelia can be restricted to either the apical or the basolateral plasma membrane. Polarized virus release is assumed to significantly influence viral pathogenesis because only viruses which are released from the basolateral surface or can spread to cells in underlying tissues by direct cell-to-cell fusion are supposed to easily penetrate the epithelial barrier thereby entering the blood stream and causing a systemic infection. The major determinant for polarized virus spread from epithelial cells is the basolateral sorting of the viral envelope proteins which therefore possess specific targeting signals in their cytoplasmic domains.|
Nipah virus (NiV) is a highly pathogenic paramyxovirus classified as BSL-4 agent. In infected humans or animals, NiV enters via the respiratory epithelium and establishes a systemic endothelial infection. Thus, NiV is able to penetrate the epithelial barrier in the respiratory tract in vivo suggesting that the NiV glycoproteins are able to mediate basolateral virus spread. Supporting this idea, we were recently able to detect both glycoproteins on the basolateral surfaces of NiV-infected polarized epithelial. Aim of this project is to determine (1) the importance of the potential tyrosine- or leucine-based motifs in the cytoplasmic tails of the NiV glycoproteins for basolateral transport in epithelial cells and (2) the biological relevance of the basolateral glycoprotein expression for cell-to-cell fusion within epithelial cell monolayers.
|Laufzeit||01.04.2006 - 31.12.2009|
|Zugehörigkeit|| Intra- und interzellulärer Transport und Kommunikation|
DFG-Graduiertenkolleg (DFG-GRK 1216)
Vogt, C., Eickmann, M., Diederich, S., Moll, M., and A. Maisner (2005). Endocytosis of the Nipah virus glycoproteins. J. Virol. 79:3865-3872. |
Moll, M., H.-D. Klenk, G. Herrler, and A. Maisner (2001). A single amino acid change in the cytoplasmic domains of measles virus glycoproteins H and F alters targeting, endocytosis and fusion in polarized MDCK cells. J. Biol. Chem. 276:17887-17894.
Maisner, A., H.-D. Klenk and G. Herrler (1998). Polarized budding of measles virus is not determined by viral surface glycoproteins. J. Virol. 71:5276-5278.
Maisner, A., G. Zimmer, M. K. Liszewski, D. M. Lublin, J. P. Atkinson, and G. Herrler (1997). Membrane cofactor protein (MCP; CD46) is a basolateral protein that is not endocytosed: Importance of the tetrapeptide F-T-S-L at the carboxy terminus. J. Biol. Chem. 272:20793-20799.