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Journal of Virology, September 2004, p. 9552-9559, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9552-9559.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Measles Virus Interacts with and Alters Signal Transduction in T-Cell Lipid Rafts

Elita Avota, Nora Müller, Maren Klett, and Sibylle Schneider-Schaulies*

Institute for Virology and Immunobiology, University of Würzburg, Würzburg, Germany

Received 19 January 2004/ Accepted 30 April 2004

By a contact-dependent surface interaction, the measles virus (MV) glycoprotein complex induces a pronounced inhibition of T-cell proliferation. We now show that MV directly interacts with glycosphingolipid-enriched membrane microdomains on human primary T cells and alters recruitment and segregation of membrane proximal signaling components. Contact-dependent interference with T-cell receptor-stimulated tyrosine phosphorylation and Ca mobilization is a late event seen 24 h after MV treatment. In contrast, stimulated recruitment of pleckstrin homology domain-containing proteins such as Akt and Vav is inhibited early after MV contact, as is segregation of the activated Akt kinase from rafts. Tyrosine phosphorylation of the regulatory subunit of the phosphatidylinositol 3-kinase (PI3K), p85, is apparently normal then, yet this protein fails to partition to the lipid raft fraction, and this is associated with stable expression of its negative regulator Cbl-b. Thus, by interaction with lipid rafts, MV contact initially targets recruitment of PI3K by preventing stimulated Cbl-b degradation and activation of PI3K-dependent signaling components.

* Corresponding author. Mailing address: Institute for Virology and Immunobiology, University of Würzburg, Versbacher Str. 7, D-97078 Würzburg, Germany. Phone: 49-931-201-49895. Fax: 49-931-201-49553. E-mail: s-s-s{at}vim.uni-wuerzburg.de.

Journal of Virology, September 2004, p. 9552-9559, Vol. 78, No. 17
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.17.9552-9559.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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