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Journal of Virology, July 1999, p. 5265-5273, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Measles Virus Spread by Cell-Cell Contacts: Uncoupling of Contact-Mediated Receptor (CD46) Downregulation from Virus Uptake

Ruth Firsching,1 Christian J. Buchholz,2,dagger Urs Schneider,2 Roberto Cattaneo,2,Dagger Volker ter Meulen,1 and Jürgen Schneider-Schaulies1,*

Institut für Virologie und Immunbiologie, D-97078 Würzburg, Germany,1 and Institut für Molekularbiologie, CH-8057 Zürich, Switzerland2

Received 14 December 1998/Accepted 16 March 1999

CD46, which serves as a receptor for measles virus (MV; strain Edmonston), is rapidly downregulated from the cell surface after contact with viral particles or infected cells. We show here that the same two CD46 complement control protein (CCP) domains responsible for primary MV attachment mediate its downregulation. Optimal downregulation efficiency was obtained with CD46 recombinants containing CCP domains 1 and 2, whereas CCP 1, alone and duplicated, induced a slight downregulation. Using persistently infected monocytic/promyelocytic U937 cells which release very small amounts of infectious virus, and uninfected HeLa cells as contact partners, we then showed that during contact the formation of CD46-containing patches and caps precedes CD46 internalization. Nevertheless, neither substances inhibiting capping nor the fusion-inhibiting peptide Z-D-Phe-L-Phe-Gly-OH (FIP) blocked CD46 downregulation. Thus, CD46 downregulation can be uncoupled from fusion and subsequent virus uptake. Interestingly, in that system cell-cell contacts lead to a remarkably efficient infection of the target cells which is only partially inhibited by FIP. The finding that the contact of an infected with uninfected cells results in transfer of infectious viral material without significant (complete) fusion of the donor with the recipient cell suggests that microfusion events and/or FIP-independent mechanisms may mediate the transfer of MV infectivity from cell to cell.

* Corresponding author. Mailing address: Institut für Virologie und Immunbiologie, Versbacher Str. 7, D-97078 Würzburg, Germany. Phone: 0931-2015954. Fax: 0931-2013934. E-mail: jss{at}vim.uni-wuerzburg.de.

dagger Present address: Paul-Ehrlich-Institut, Abt. Med. Biotechnologie, D-63225 Langen, Germany.

Dagger Present address: Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905.

Journal of Virology, July 1999, p. 5265-5273, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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