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Journal of Virology, April 2003, p. 3913-3921, Vol. 77, No. 7
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.7.3913-3921.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
4ß1 Integrin Acts as a Cell Receptor for Murine Polyomavirus at the Postattachment Level
Maddalena Caruso, Laura Belloni,
Olga Sthandier, Paolo Amati,* and Marie-Isabelle Garcia*
Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Istituto Pasteur-Fondazione Cenci Bolognetti, Università di Roma "La Sapienza," 00161 Rome, Italy
Received 13 September 2002/
Accepted 18 December 2002
The initial interaction of murine polyomavirus (Py) with host cells occurs through direct binding of the major capsid protein VP1 with cell membrane molecules containing terminal sialic acids; however, these Py receptor molecules have not yet been identified. Analysis of the capsid protein primary sequences of all murine strains revealed the presence of integrin ligand motifs in the DE and EF loops of VP1 (LDV and DLXXL, respectively) and at the N terminus of VP2 (DGE). We show that infectivity of the Py A2 strain in mouse Swiss 3T3 fibroblasts is significantly reduced only in the presence of natural integrin ligands carrying an LDV motif or antibodies directed against the
4 and ß1 integrin subunits. Furthermore, we demonstrate that expression of the
4 subunit in the
4-deficient BALB/c 3T3 cells increases viral infectivity. Addition of
4 function-blocking antibodies, prior to or after virus adsorption, blocks this increased infectivity without affecting virus binding to cells. Taken together, these data indicate that expression of
4 integrin enhances permissivity to Py, probably by acting as one of the postattachment receptors.
* Corresponding author. Mailing address: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma "La Sapienza," Viale Regina Elena 324, 00161 Rome, Italy. Phone: 39 06490393. Fax: 39 064462891. E-mail for Paolo Amati:
amati{at}bce.uniroma1.it.
* Corresponding author. Mailing address: Dipartimento di Biotecnologie Cellulari ed Ematologia, Sezione di Genetica Molecolare, Università di Roma "La Sapienza," Viale Regina Elena 324, 00161 Rome, Italy. Phone: 39 06490393. Fax: 39 064462891. E-mail for Paolo Amati: garcia{at}bce.uniroma1.it.
Present address: Fondazione Andrea Cisalpino, Lab. Espressione Genica, Policlinico "Umberto I," Università di Roma "La Sapienza," 00161 Rome, Italy.
Journal of Virology, April 2003, p. 3913-3921, Vol. 77, No. 7
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.7.3913-3921.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
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