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Originally published In Press as doi:10.1074/jbc.M511572200 on February 15, 2006

J. Biol. Chem., Vol. 281, Issue 15, 10243-10249, April 14, 2006
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Identification of the Segments of the Mouse Transferrin Receptor 1 Required for Mouse Mammary Tumor Virus Infection*Formula

Enxiu Wang{ddagger}, Lorraine Albritton§, and Susan R. Ross{ddagger}1

From the {ddagger}Department of Microbiology and Abramson Family Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104 and §Department of Molecular Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163

Most enveloped viruses enter cells through binding of virion surface envelope proteins to receptors found on the plasma membrane of the cell. The beta retrovirus mouse mammary tumor virus (MMTV) uses transferrin receptor 1 (TfR1) to enter cells in a pH-dependent mechanism, probably co-trafficking with TfR1 to an acidic compartment where virus entry occurs. We have shown here that, although mouse and rat TfR1 function as entry receptors, cat, dog, hamster, or human TfR1s do not support MMTV infection. We also demonstrated that MMTV entry is independent of transferrin, iron, and the TfR1 cofactor hereditary hematochromatosis HFE protein. Using chimeric mouse/human hybrid TfR1 constructs, we determined the site of interaction with MMTV and found that it maps to two segments physically disparate from the TfR and HFE binding sites. Thus, MMTV has apparently evolved to enter cells independently of the iron status of the host.


Received for publication, October 25, 2005 , and in revised form, February 15, 2006.

* This work was supported by Public Health Service Grant R01 CA73746 (to S. R. R.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Formula The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

1 To whom correspondence should be addressed: Dept. of Microbiology, University of Pennsylvania, Rm. 313BRBII/III, 421 Curie Blvd., Philadelphia, PA 19104-6142. Tel.: 215-898-9764; Fax: 215-573-2028; E-mail: rosss{at}mail.med.upenn.edu.


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