Untersuchung antiviraler Effektormechanismen und der Masernvirus-Ausbreitung in humanen Endothelzellen
Final Report Abstract
In order to analyze whether measles virus (MV) is transported via transmigrating leukocytes across endothelial barriers, or whether the virus spreads via infection of endothelial cells and basolateral release, we investigated the migratory behaviour of infected human primary T-lymphocytes across polarized cell layers of human brain microvascular endothelial cells (HBMEC). We found that the capacity of lymphocytes to migrate through filter pores was only slightly affected by wildtype MV-infection, whereas their capacity to migrate through endothelial barriers was drastically reduced. MV-infection stimulated the expression and activation of the leukocyte integrins LFA-1 and VLA-4 mediating a strong adherence to the surface of endothelial cells. Furthermore, the formation of engulfing membrane protrusions by endothelial cells, so called transmigratory cups, was induced, but transmigration was impaired. As a consequence of this close cell-cell contact, MV-infection was transmitted from lymphocytes to the endothelium. MV-envelope-proteins were expressed on the apical and basolateral surface of infected polarized endothelial cells, and virus was released from both sides. Wildtype MV-infection did not induce the formation of syncytia suggesting virus spread from cell to cell via cell processes and contacts. Our data indicate that transendothelial migration of infected T-cells is strongly inhibited, whereas virus can cross endothelial barriers by productive infection of the endothelium and subsequent bipolar virus release.
Publications
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(2003). CD46- and CD150-independent endothelial cell infection with wildtype measles viruses. J.Gen. Virol. 84:1189-1-197
Andres, O., Obojes, K., Kim, K.S., ter Meulen, V., and Schneider-Schaulies, J.
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(2003). Measles and its neurological complications. Clinical Neurovirology. Ed.: A. Nath, J.R. Berger. pp 401-430
Weissbrich, B., Schneider-Schaulies, J. and ter Meulen V.
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(2005). Indolamine 2,3-dioxygenase (IDO) mediates cell type specific anti-measles virus activity of gamma interferon. J. Virol. 79: 7768-7776
Obojes, K., Andres, O., Kim, K.S., Däubener, W. and Schneider-Schaulies, J.
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(2006). Regulation of human endogenous retrovirus W protein expression by herpes simplex virus type 1: Implications for multiple sclerosis. J. Neurovirol. 12:65-71
Ruprecht, K., Obojes, K., Wengel, V., Gronen, F., Perron, H., Schneider-Schaulies, J., and Rieckmann, P.
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(2008). Measles virus-induced block of transendothelial migration of T lymphocytes and infection-mediated virus spread across endothelial cell barriers. J. Virol., 82: 11273-11282
Dittmar, S., Harms, H., Runkler, N., Maisner, A., Kim, K.S., and Schneider-Schaulies, J.
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(2008). Receptor interactions, tropism, and mechanisms involved in morbillivirus-induced immunomodulation. Advances in Virus Research, 71: 173-205
Schneider-Schaulies, J., and Schneider-Schaulies, S.
