Role of a Third Extracellular Domain of an Ecotropic Receptor in Moloney Murine Leukemia Virus Infection

  • Bae Eun-Hye (Department of Microbiology and Institute of Basic Science, Dankook University) ;
  • Park Sung-Han (Department of Microbiology and Institute of Basic Science, Dankook University) ;
  • Jung Yong-Tae (Department of Microbiology and Institute of Basic Science, Dankook University)
  • Published : 2006.08.01

Abstract

The murine ecotropic retroviral receptor has been demonstrated to function as a mouse cationic amino acid transporter 1(mCAT1), and is comprised of multiple membranespanning domains. Feral mouse (Mus dunni) cells are not susceptible to infection by the ecotropic Moloney murine leukemia virus (MoMLV), although they can be infected by other ecotropic murine leukemia viruses, including Friend MLV and Rauscher MLV. The relative inability of MoMLV to replicate in M. dunni cells has been attributed to two amino acids $(V_{214}\;and\;G_{236})$ located within the third extracellular loop of the M. dunni CAT1 receptor (dCAT1). Via the exchange of the third extracellular loop of the mCAT1 cDNA encoding receptor from the permissive mouse and the corresponding portion of cDNA encoding for the nonpermissive M. dunni receptor, we have identified the most critical amino acid residue, which is a glycine located at position 236 within the third extracellular loop of dCAT1. We also attempted to determine the role of the third extracellular loop of the M. dunni CAT1 receptor with regard to the formation of the syncytium. The relationship between dCAT1 and virus-induced syncytia was suggested initially by our previous identification of two MLV isolates (S82F in Moloney and S84A in Friend MLV), both of which are uniquely cytopathic in M. dunni cells. In an attempt to determine the relationship existing between dCAT1 and the virally-induced syncytia, we infected 293-dCAT1 or chimeric dCAT1 cells with the S82F pseudotype virus. The S82F pseudotype virus did not induce the formation of syncytia, but did show increased susceptibility to 293 cells expressing dCATl. The results of our study indicate that S82F-induced syncytium formation may be the result of cell-cell fusion, but not virus-cell fusion.

Keywords

References

  1. Albritton, L.M., L. Tseng, D. Scaden, and J.M. Cunningham. 1989. A putative murine ecotropic retrovirus receptor gene encodes a multiple membrane-spanning protein and confers susceptibility to virus infection. Cell 57, 659-666 https://doi.org/10.1016/0092-8674(89)90134-7
  2. Albritton, L.M., J.W. Kim, L. Tseng, and J.M. Cunningham. 1993. Envelope-binding domain in the cationic amino acid transporter determines the host range of ecotropic murine retroviruses. J. Virol. 67, 2091-2096
  3. Chung, M., K. Kizhatil, L.M. Albritton, and G.N. Gaulton. 1999. Induction of syncytia by neuropathogenic murine leukemia viruses depends on receptor density, host cell determinants, and the intrinsic fusion potential of envelope protein. J. Virol. 73, 9377-9385
  4. Davey, R.A., C.A. Hamson, J.J. Healey, and J.M. Cunningham. 1997. In vitro binding of purified murine ecotropic retrovirus envelope surface protein to its receptor, MCAT-1. J. Virol. 71, 8096-8102
  5. Davey, R.A., Y. Zuo, and J.M. Cunningham. 1999. Identification of a receptor-binding pocket on the envelope protein of Friend murine leukemia virus. J. Virol. 73, 3758-3763
  6. Eiden, M.V., K. Farrell, and C.A. Wilson. 1994. Glycosylationdependent inactivation of the ecotropic murine leukemia virus receptor. J. Virol. 68, 626-631
  7. Eiden, M.V., K. Farrell, J. Warsowe, L.C. Mahan, and C.A. Wilson. 1993. Characterization of a naturally occurring ecotropic receptor that does not facilitate entry of all ecotropic murine retroviruses. J. Virol. 67, 4056-4061
  8. Fass, D., R.A. Davey, C.A. Hamson, P.S. Kim, J.M. Cunningham, and J.M. Berger. 1997. Structure of a murine leukemia virus receptor-binding glycoprotein at 2.0 angstrom resolution. Science 277, 1662-1666 https://doi.org/10.1126/science.277.5332.1662
  9. Jones, J.S. and R. Risser. 1993. Cell fusion induced by the murine leukemia virus envelope glycoprotein. J. Virol. 67, 67-74
  10. Jung, Y.T. and C.A. Kozak. 2003. Generation of novel syncytium-inducing and host range variants of ecotropic Moloney murine leukemia virus in Mus spicilegus. J. Virol. 77, 5065-5072 https://doi.org/10.1128/JVI.77.9.5065-5072.2003
  11. Jung, Y.T., T. Wu, and C.A. Kozak. 2004. Novel host range and cytopathic variant of ecotropic Friend murine leukemia virus. J. Virol. 78, 12189-12197 https://doi.org/10.1128/JVI.78.22.12189-12197.2004
  12. Kim, J.W., E.I. Closs, L.M. Albritton, and J. M. Cunningham. 1991. Transport of cationic amino acids by the mouse ecotropic retrovirus receptor. Nature 352, 725-728 https://doi.org/10.1038/352725a0
  13. Kim, J.W. and J.M. Cunningham. 1993. N-linked glycosylation of the receptor for murine ecotropic retroviruses is altered in virus-infected cells. J. Biol. Chem. 268, 16316-16320
  14. Masuda, M., N. Kakushima, S.G. Wilt, S.K. Ruscetti, P.M. Hoffman, A. Iwamoto, and M. Masuda. 1999. Analysis of receptor usage by ecotropic murine retroviruses, using green fluorescent protein-tagged cationic amino acid transporters. J. Virol. 73, 8623-8629
  15. Miller, D.G. and A.D. Miller. 1992. Tunicamycin treatment of CHO cells abrogates multiple blocks to retrovirus infection, one of which is due to a secreted inhibitor. J. Virol. 66, 78-84
  16. Ou, W. and J. Silver. 2003. Role of a conserved aminoterminal sequence in the ecotropic MLV receptor mCAT1. Virology. 308, 101-108 https://doi.org/10.1016/S0042-6822(02)00086-7
  17. Park, B.H., B. Matuschke, E. Lavi, and G.N. Gaulton. 1994. A point mutation in the env gene of a murine leukemia virus induced syncytium formation and neurologic disease. J. Virol. 68, 7516-7524
  18. Rein, A., A.M. Schultz, J.P. Bader, and R.H. Bassin. 1982. Inhibitors of glycosylation reverse retroviral interference. Virology 119, 185-192 https://doi.org/10.1016/0042-6822(82)90075-7
  19. Siess, D.C., S.L. Kozak, and D. Kabat. 1996. Exceptional fusogenicity of Chinese hamster ovary cells with murine retroviruses suggests roles for cellular factor(s) and receptor clusters in the membrane fusion process. J. Virol. 70, 3432-3439
  20. Tavoloni, N. and A. Rudenholz. 1997. Variable efficiency of murine leukemia retroviral vector on mammalian cells: role of cellular glycosylation. Virology 229, 49-56 https://doi.org/10.1006/viro.1996.8412
  21. Yoshimoto, T., E. Yoshimoto, and D. Meruelo. 1993. Identification of amino acid residues critical for infection with ecotropic murine leukemia retrovirus. J. Virol. 67, 1310-1314
  22. Wang, H., M.P. Kavanaugh, R.A. North, and D. Kabat. 1991. Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter. Nature 352, 729-731 https://doi.org/10.1038/352729a0
  23. White, J., M. Kielian, and A. Helenius. 1983. Membrane fusion proteins of enveloped animal viruses. Q. Rev. Biophys. 16, 151-195 https://doi.org/10.1017/S0033583500005072