Identification of the segments of the mouse transferrin receptor 1 required for mouse mammary tumor virus infection.
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.
Department of Microbiology and Abramson Family Cancer Center, University of Pennsylvania, Rm. 313 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Enxiu
E
Wang
Lorraine
L
Albritton
Susan R
SR
Ross
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D015153:Blotting, Western; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000737:chemistry; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics*; D008565:Membrane Proteins / Q000737:chemistry; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009842:Oligopeptides / Q000737:chemistry; D011485:Protein Binding; D051381:Rats; D011990:Receptors, Transferrin / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D014168:Transferrin / Q000737:chemistry
D000071020:Hemochromatosis Protein; C499535:Hfe protein, mouse; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D009842:Oligopeptides; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D014168:Transferrin; C047981:arginyl-glycyl-aspartic acid; D007501:Iron