Previous Article | Next Article 
Journal of Virology, February 2003, p. 2717-2729, Vol. 77, No. 4
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.4.2717-2729.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
Structure and Mechanism of a Coreceptor for Infection by a Pathogenic Feline Retrovirus
Anna L. Barnett,1 David L. Wensel,1 Weihua Li,1 Deborah Fass,2* and James M. Cunningham1*
Department of Medicine and Howard Hughes Medical Institute, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115,1
Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel2
Received 17 June 2002/
Accepted 2 November 2002
Infection of T lymphocytes by the cytopathic retrovirus feline leukemia virus subgroup T (FeLV-T) requires FeLIX, a cellular coreceptor that is encoded by an endogenous provirus and closely resembles the receptor-binding domain (RBD) of feline leukemia virus subgroup B (FeLV-B). We determined the structure of FeLV-B RBD, which has FeLIX activity, to a 2.5-Å resolution by X-ray crystallography. The structure of the receptor-specific subdomain of this glycoprotein differs dramatically from that of Friend murine leukemia virus (Fr-MLV), which binds a different cell surface receptor. Remarkably, we find that Fr-MLV RBD also activates FeLV-T infection of cells expressing the Fr-MLV receptor and that FeLV-B RBD is a competitive inhibitor of infection under these conditions. These studies suggest that FeLV-T infection relies on the following property of mammalian leukemia virus RBDs: the ability to couple interaction with one of a variety of receptors to the activation of a conserved membrane fusion mechanism. A comparison of the FeLV-B and Fr-MLV RBD structures illustrates how receptor-specific regions are linked to conserved elements critical for postbinding events in virus entry.
* Corresponding author. Mailing address for James M. Cunningham: Rm. 1030, Thorn Building, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115. Phone: (617) 732-5852. Fax: (617) 738-5575. E-mail:
cunningham{at}rascal.med.harvard.edu. Mailing address for Deborah Fass: Department of Structural Biology, Weizmann Institute of Science, Rehovot 76100, Israel. Phone: 011-8-9343214. Fax: 011-8-9344136. E-mail: deborah.fass@weizmann.ac.il.
Journal of Virology, February 2003, p. 2717-2729, Vol. 77, No. 4
0022-538X/03/$08.00+0 DOI: 10.1128/JVI.77.4.2717-2729.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.
This article has been cited by other articles:
-
Sarangi, A., Bupp, K., Roth, M. J.
(2007). Identification of a retroviral receptor used by an Envelope protein derived by peptide library screening. Proc. Natl. Acad. Sci. USA
104: 11032-11037
[Abstract]
[Full Text]
-
Kuhn, J. H., Radoshitzky, S. R., Guth, A. C., Warfield, K. L., Li, W., Vincent, M. J., Towner, J. S., Nichol, S. T., Bavari, S., Choe, H., Aman, M. J., Farzan, M.
(2006). Conserved Receptor-binding Domains of Lake Victoria Marburgvirus and Zaire Ebolavirus Bind a Common Receptor. J. Biol. Chem.
281: 15951-15958
[Abstract]
[Full Text]
-
Cheng, H. H., Anderson, M. M., Hankenson, F. C., Johnston, L., Kotwaliwale, C. V., Overbaugh, J.
(2006). Envelope Determinants for Dual-Receptor Specificity in Feline Leukemia Virus Subgroup A and T Variants. J. Virol.
80: 1619-1628
[Abstract]
[Full Text]
-
Bahrami, S., Duch, M., Pedersen, F. S.
(2004). Change of Tropism of SL3-2 Murine Leukemia Virus, Using Random Mutational Libraries. J. Virol.
78: 9343-9351
[Abstract]
[Full Text]
-
Lavillette, D., Kabat, D.
(2004). Porcine Endogenous Retroviruses Infect Cells Lacking Cognate Receptors by an Alternative Pathway: Implications for Retrovirus Evolution and Xenotransplantation. J. Virol.
78: 8868-8877
[Abstract]
[Full Text]
-
O'Reilly, L., Roth, M. J.
(2003). G541R within the 4070A TM Protein Regulates Fusion in Murine Leukemia Viruses. J. Virol.
77: 12011-12021
[Abstract]
[Full Text]
-
Lu, C.-W., Roth, M. J.
(2003). Role of the Mutation Q252R in Activating Membrane Fusion in the Murine Leukemia Virus Surface Envelope Protein. J. Virol.
77: 10841-10849
[Abstract]
[Full Text]
-
Wensel, D. L., Li, W., Cunningham, J. M.
(2003). A Virus-Virus Interaction Circumvents the Virus Receptor Requirement for Infection by Pathogenic Retroviruses. J. Virol.
77: 3460-3469
[Abstract]
[Full Text]