Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1991 Dec;65(12):6468–6477. doi: 10.1128/jvi.65.12.6468-6477.1991

Plasma membrane receptors for ecotropic murine retroviruses require a limiting accessory factor.

H Wang 1, R Paul 1, R E Burgeson 1, D R Keene 1, D Kabat 1
PMCID: PMC250689  PMID: 1942243

Abstract

A retroviral vector was used to express various amounts of the receptor (ecoR) for ecotropic host range murine retroviruses on naturally barren hamster, mink, and human cells. These cells and murine cells were then incubated for 2 h with dilutions of a helper-free ecotropic retrovirus that encodes human growth hormone, and the number of infected cells was later determined by growth hormone-specific immunofluorescence. For all cells under the conditions of these studies, virus adsorption was the limiting step of infection and the cellular capacities for infection were unsaturated either at cell surfaces or at intracellular sites. Thus, infections occurred at low multiplicities of infection per cell and were directly proportional to virus and cell concentrations, and only a small percentage (ca. 5%) of the infectious virions became adsorbed from the medium during the 2-h incubations. Although increasing the adsorption by raising virus or cell concentrations results in more infections in the cultures, increasing adsorption by raising the number of ecoR above a low threshold had no effect on infections. Thus, cells with a low number of ecoR were infected as efficiently as highly adsorbing cells that contained many times more ecoR. To reconcile these results, we conclude that only a small, set number of cell surface ecoR can be functional for infection and that all excess ecoR can only bind virus into an unsalvageable pool. Therefore, retroviral receptors on single cells are functionally diverse. Our results suggest that activity of ecoR in infection requires a limiting second cellular component.

Full text

PDF
6468

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albritton L. M., Tseng L., Scadden D., Cunningham J. M. A putative murine ecotropic retrovirus receptor gene encodes a multiple membrane-spanning protein and confers susceptibility to virus infection. Cell. 1989 May 19;57(4):659–666. doi: 10.1016/0092-8674(89)90134-7. [DOI] [PubMed] [Google Scholar]
  2. Bassin R. H., Ruscetti S., Ali I., Haapala D. K., Rein A. Normal DBA/2 mouse cells synthesize a glycoprotein which interferes with MCF virus infection. Virology. 1982 Nov;123(1):139–151. doi: 10.1016/0042-6822(82)90301-4. [DOI] [PubMed] [Google Scholar]
  3. Bestwick R. K., Kozak S. L., Kabat D. Overcoming interference to retroviral superinfection results in amplified expression and transmission of cloned genes. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5404–5408. doi: 10.1073/pnas.85.15.5404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cao Y. Z., Friedman-Kien A. E., Huang Y. X., Li X. L., Mirabile M., Moudgil T., Zucker-Franklin D., Ho D. D. CD4-independent, productive human immunodeficiency virus type 1 infection of hepatoma cell lines in vitro. J Virol. 1990 Jun;64(6):2553–2559. doi: 10.1128/jvi.64.6.2553-2559.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chesebro B., Buller R., Portis J., Wehrly K. Failure of human immunodeficiency virus entry and infection in CD4-positive human brain and skin cells. J Virol. 1990 Jan;64(1):215–221. doi: 10.1128/jvi.64.1.215-221.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cianciolo G. J., Copeland T. D., Oroszlan S., Snyderman R. Inhibition of lymphocyte proliferation by a synthetic peptide homologous to retroviral envelope proteins. Science. 1985 Oct 25;230(4724):453–455. doi: 10.1126/science.2996136. [DOI] [PubMed] [Google Scholar]
  7. Clapham P. R., Weber J. N., Whitby D., McIntosh K., Dalgleish A. G., Maddon P. J., Deen K. C., Sweet R. W., Weiss R. A. Soluble CD4 blocks the infectivity of diverse strains of HIV and SIV for T cells and monocytes but not for brain and muscle cells. Nature. 1989 Jan 26;337(6205):368–370. doi: 10.1038/337368a0. [DOI] [PubMed] [Google Scholar]
  8. Cone R. D., Mulligan R. C. High-efficiency gene transfer into mammalian cells: generation of helper-free recombinant retrovirus with broad mammalian host range. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6349–6353. doi: 10.1073/pnas.81.20.6349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DeLarco J., Todaro G. J. Membrane receptors for murine leukemia viruses: characterization using the purified viral envelope glycoprotein, gp71. Cell. 1976 Jul;8(3):365–371. doi: 10.1016/0092-8674(76)90148-3. [DOI] [PubMed] [Google Scholar]
  10. Delwart E. L., Panganiban A. T. Role of reticuloendotheliosis virus envelope glycoprotein in superinfection interference. J Virol. 1989 Jan;63(1):273–280. doi: 10.1128/jvi.63.1.273-280.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Evans L. H., Dresler S., Kabat D. Synthesis and glycosylation of polyprotein precursors to the internal core proteins of Friend murine leukemia virus. J Virol. 1977 Dec;24(3):865–874. doi: 10.1128/jvi.24.3.865-874.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fitting T., Kabat D. Evidence for a glycoprotein "signal" involved in transport between subcellular organelles. Two membrane glycoproteins encoded by murine leukemia virus reach the cell surface at different rates. J Biol Chem. 1982 Dec 10;257(23):14011–14017. [PubMed] [Google Scholar]
  13. Gazzolo L., Duc Dodon M. Direct activation of resting T lymphocytes by human T-lymphotropic virus type I. Nature. 1987 Apr 16;326(6114):714–717. doi: 10.1038/326714a0. [DOI] [PubMed] [Google Scholar]
  14. Handelin B. L., Kabat D. Cell surface receptors for murine leukemia viruses: two assays and their implications. Virology. 1985 Jan 15;140(1):183–187. doi: 10.1016/0042-6822(85)90458-1. [DOI] [PubMed] [Google Scholar]
  15. Hartley J. W., Rowe W. P. Naturally occurring murine leukemia viruses in wild mice: characterization of a new "amphotropic" class. J Virol. 1976 Jul;19(1):19–25. doi: 10.1128/jvi.19.1.19-25.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hebebrand L. C., Mathes L. E., Olsen R. G. Inhibition of concanavalin A stimulation of feline lymphocytes by inactivated feline leukemia virus. Cancer Res. 1977 Dec;37(12):4532–4533. [PubMed] [Google Scholar]
  17. Ikeda H., Sugimura H. Fv-4 resistance gene: a truncated endogenous murine leukemia virus with ecotropic interference properties. J Virol. 1989 Dec;63(12):5405–5412. doi: 10.1128/jvi.63.12.5405-5412.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kabat D. Cell surface receptors for ecotropic murine retroviruses: mobile membrane proteins that mediate binding and slow endocytosis of the viral envelope glycoprotein. Virology. 1989 Aug;171(2):467–474. doi: 10.1016/0042-6822(89)90616-8. [DOI] [PubMed] [Google Scholar]
  19. Kabat D. Molecular biology of Friend viral erythroleukemia. Curr Top Microbiol Immunol. 1989;148:1–42. doi: 10.1007/978-3-642-74700-7_1. [DOI] [PubMed] [Google Scholar]
  20. Kleinerman E. S., Lachman L. B., Knowles R. D., Snyderman R., Cianciolo G. J. A synthetic peptide homologous to the envelope proteins of retroviruses inhibits monocyte-mediated killing by inactivating interleukin 1. J Immunol. 1987 Oct 1;139(7):2329–2337. [PubMed] [Google Scholar]
  21. Kozak C. A., Albritton L. M., Cunningham J. Genetic mapping of a cloned sequence responsible for susceptibility to ecotropic murine leukemia viruses. J Virol. 1990 Jun;64(6):3119–3121. doi: 10.1128/jvi.64.6.3119-3121.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kozak C. A. Genetic mapping of a mouse chromosomal locus required for mink cell focus-forming virus replication. J Virol. 1983 Oct;48(1):300–303. doi: 10.1128/jvi.48.1.300-303.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kozak C. A. Susceptibility of wild mouse cells to exogenous infection with xenotropic leukemia viruses: control by a single dominant locus on chromosome 1. J Virol. 1985 Sep;55(3):690–695. doi: 10.1128/jvi.55.3.690-695.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kozak S. L., Kabat D. Ping-pong amplification of a retroviral vector achieves high-level gene expression: human growth hormone production. J Virol. 1990 Jul;64(7):3500–3508. doi: 10.1128/jvi.64.7.3500-3508.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Li J. P., Bestwick R. K., Spiro C., Kabat D. The membrane glycoprotein of Friend spleen focus-forming virus: evidence that the cell surface component is required for pathogenesis and that it binds to a receptor. J Virol. 1987 Sep;61(9):2782–2792. doi: 10.1128/jvi.61.9.2782-2792.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Li J. P., D'Andrea A. D., Lodish H. F., Baltimore D. Activation of cell growth by binding of Friend spleen focus-forming virus gp55 glycoprotein to the erythropoietin receptor. Nature. 1990 Feb 22;343(6260):762–764. doi: 10.1038/343762a0. [DOI] [PubMed] [Google Scholar]
  27. Li X. L., Moudgil T., Vinters H. V., Ho D. D. CD4-independent, productive infection of a neuronal cell line by human immunodeficiency virus type 1. J Virol. 1990 Mar;64(3):1383–1387. doi: 10.1128/jvi.64.3.1383-1387.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lifson J. D., Reyes G. R., McGrath M. S., Stein B. S., Engleman E. G. AIDS retrovirus induced cytopathology: giant cell formation and involvement of CD4 antigen. Science. 1986 May 30;232(4754):1123–1127. doi: 10.1126/science.3010463. [DOI] [PubMed] [Google Scholar]
  29. Lyerly H. K., Matthews T. J., Langlois A. J., Bolognesi D. P., Weinhold K. J. Human T-cell lymphotropic virus IIIB glycoprotein (gp120) bound to CD4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4601–4605. doi: 10.1073/pnas.84.13.4601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Maddon P. J., Dalgleish A. G., McDougal J. S., Clapham P. R., Weiss R. A., Axel R. The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell. 1986 Nov 7;47(3):333–348. doi: 10.1016/0092-8674(86)90590-8. [DOI] [PubMed] [Google Scholar]
  31. Maddon P. J., McDougal J. S., Clapham P. R., Dalgleish A. G., Jamal S., Weiss R. A., Axel R. HIV infection does not require endocytosis of its receptor, CD4. Cell. 1988 Sep 9;54(6):865–874. doi: 10.1016/s0092-8674(88)91241-x. [DOI] [PubMed] [Google Scholar]
  32. Mann R., Mulligan R. C., Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell. 1983 May;33(1):153–159. doi: 10.1016/0092-8674(83)90344-6. [DOI] [PubMed] [Google Scholar]
  33. Mathes L. E., Olsen R. G., Hebebrand L. C., Hoover E. A., Schaller J. P. Abrogation of lymphocyte blastogenesis by a feline leukaemia virus protein. Nature. 1978 Aug 17;274(5672):687–689. doi: 10.1038/274687a0. [DOI] [PubMed] [Google Scholar]
  34. McDougal J. S., Kennedy M. S., Sligh J. M., Cort S. P., Mawle A., Nicholson J. K. Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule. Science. 1986 Jan 24;231(4736):382–385. doi: 10.1126/science.3001934. [DOI] [PubMed] [Google Scholar]
  35. McGrath M. S., Pillemer E., Kooistra D., Weissman I. L. The role of MuLV receptors on T-lymphoma cells in lymphoma cell proliferation. Contemp Top Immunobiol. 1980;11:157–184. doi: 10.1007/978-1-4684-3701-0_5. [DOI] [PubMed] [Google Scholar]
  36. Miller A. D., Law M. F., Verma I. M. Generation of helper-free amphotropic retroviruses that transduce a dominant-acting, methotrexate-resistant dihydrofolate reductase gene. Mol Cell Biol. 1985 Mar;5(3):431–437. doi: 10.1128/mcb.5.3.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. O'Hara B., Johann S. V., Klinger H. P., Blair D. G., Rubinson H., Dunn K. J., Sass P., Vitek S. M., Robins T. Characterization of a human gene conferring sensitivity to infection by gibbon ape leukemia virus. Cell Growth Differ. 1990 Mar;1(3):119–127. [PubMed] [Google Scholar]
  38. Oie H. K., Russell E. K., Dotson J. H., Rhoads J. M., Gazdar A. F. Host-range properties of murine xenotropic and ecotropic type-C viruses. J Natl Cancer Inst. 1976 Feb;56(2):423–426. doi: 10.1093/jnci/56.2.423. [DOI] [PubMed] [Google Scholar]
  39. Pauza C. D., Price T. M. Human immunodeficiency virus infection of T cells and monocytes proceeds via receptor-mediated endocytosis. J Cell Biol. 1988 Sep;107(3):959–968. doi: 10.1083/jcb.107.3.959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Poss M. L., Mullins J. I., Hoover E. A. Posttranslational modifications distinguish the envelope glycoprotein of the immunodeficiency disease-inducing feline leukemia virus retrovirus. J Virol. 1989 Jan;63(1):189–195. doi: 10.1128/jvi.63.1.189-195.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rasheed S., Gardner M. B., Chan E. Amphotropic host range of naturally occuring wild mouse leukemia viruses. J Virol. 1976 Jul;19(1):13–18. doi: 10.1128/jvi.19.1.13-18.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Resnick-Roguel N., Eldor A., Burstein H., Hy-Am E., Vlodavsky I., Panet A., Blajchman M. A., Kotler M. Envelope glycoprotein of avian hemangioma retrovirus induces a thrombogenic surface on human and bovine endothelial cells. J Virol. 1990 Aug;64(8):4029–4032. doi: 10.1128/jvi.64.8.4029-4032.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Riedel N., Hoover E. A., Dornsife R. E., Mullins J. I. Pathogenic and host range determinants of the feline aplastic anemia retrovirus. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2758–2762. doi: 10.1073/pnas.85.8.2758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sattentau Q. J., Weiss R. A. The CD4 antigen: physiological ligand and HIV receptor. Cell. 1988 Mar 11;52(5):631–633. doi: 10.1016/0092-8674(88)90397-2. [DOI] [PubMed] [Google Scholar]
  45. Simon M. C., Neckameyer W. S., Hayward W. S., Smith R. E. Genetic determinants of neoplastic diseases induced by a subgroup F avian leukosis virus. J Virol. 1987 Apr;61(4):1203–1212. doi: 10.1128/jvi.61.4.1203-1212.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Sitbon M., Sola B., Evans L., Nishio J., Hayes S. F., Nathanson K., Garon C. F., Chesebro B. Hemolytic anemia and erythroleukemia, two distinct pathogenic effects of Friend MuLV: mapping of the effects to different regions of the viral genome. Cell. 1986 Dec 26;47(6):851–859. doi: 10.1016/0092-8674(86)90800-7. [DOI] [PubMed] [Google Scholar]
  47. Sodroski J., Goh W. C., Rosen C., Campbell K., Haseltine W. A. Role of the HTLV-III/LAV envelope in syncytium formation and cytopathicity. 1986 Jul 31-Aug 6Nature. 322(6078):470–474. doi: 10.1038/322470a0. [DOI] [PubMed] [Google Scholar]
  48. Stein B. S., Gowda S. D., Lifson J. D., Penhallow R. C., Bensch K. G., Engleman E. G. pH-independent HIV entry into CD4-positive T cells via virus envelope fusion to the plasma membrane. Cell. 1987 Jun 5;49(5):659–668. doi: 10.1016/0092-8674(87)90542-3. [DOI] [PubMed] [Google Scholar]
  49. Stevenson M., Meier C., Mann A. M., Chapman N., Wasiak A. Envelope glycoprotein of HIV induces interference and cytolysis resistance in CD4+ cells: mechanism for persistence in AIDS. Cell. 1988 May 6;53(3):483–496. doi: 10.1016/0092-8674(88)90168-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Strand M., August J. T. Structural proteins of ribonucleic acid tumor viruses. Purification of envelope, core, and internal components. J Biol Chem. 1976 Jan 25;251(2):559–564. [PubMed] [Google Scholar]
  51. Szurek P. F., Yuen P. H., Jerzy R., Wong P. K. Identification of point mutations in the envelope gene of Moloney murine leukemia virus TB temperature-sensitive paralytogenic mutant ts1: molecular determinants for neurovirulence. J Virol. 1988 Jan;62(1):357–360. doi: 10.1128/jvi.62.1.357-360.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Tersmette M., van Dongen J. J., Clapham P. R., de Goede R. E., Wolvers-Tettero I. L., Geurts van Kessel A., Huisman J. G., Weiss R. A., Miedema F. Human immunodeficiency virus infection studied in CD4-expressing human-murine T-cell hybrids. Virology. 1989 Feb;168(2):267–273. doi: 10.1016/0042-6822(89)90266-3. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES