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Journal of Virology, June 2002, p. 5720-5728, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5720-5728.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Measles Virus Spreads in Rat Hippocampal Neurons by Cell-to-Cell Contact and in a Polarized Fashion

Markus U. Ehrengruber,1 Elisabeth Ehler,2 Martin A. Billeter,3 and Hussein Y. Naim3*

Brain Research Institute,1 Institute of Molecular Biology, University of Zurich, CH-8057 Zurich,3 Institute of Cell Biology, Swiss Federal Institute of Technology, CH-8093 Zurich, Switzerland2

Received 14 December 2001/ Accepted 1 March 2002

Measles virus (MV) can infect the central nervous system and, in rare cases, causes subacute sclerosing panencephalitis, characterized by a progressive degeneration of neurons. The route of MV transmission in neurons was investigated in cultured rat hippocampal slices by using MV expressing green fluorescent protein. MV infected hippocampal neurons and spread unidirectionally, in a retrograde manner, from CA1 to CA3 pyramidal cells and from there to the dentate gyrus. Spreading of infection depended on cell-to-cell contact and occurred without any detectable release of infectious particles. The role of the viral proteins in the retrograde MV transmission was determined by investigating their sorting in infected pyramidal cells. MV glycoproteins, the fusion protein (F) and hemagglutinin (H), the matrix protein (M), and the phosphoprotein (P), which is part of the viral ribonucleoprotein complex, were all sorted to the dendrites. While M, P, and H proteins remained more intracellular, the F protein localized to prominent, spine-type domains at the surface of infected cells. The detected localization of MV proteins suggests that local microfusion events may be mediated by the F protein at sites of synaptic contacts and is consistent with a mechanism of retrograde transmission of MV infection.

* Corresponding author. Mailing address: Institute of Molecular Biology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Phone: (41 1) 635 3112. Fax: (41 1) 635 6864. E-mail: naim{at}molbio.unizh.ch.

Journal of Virology, June 2002, p. 5720-5728, Vol. 76, No. 11
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.11.5720-5728.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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