Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Oct 15;93(21):11407–11413. doi: 10.1073/pnas.93.21.11407

Cell-surface receptors for retroviruses and implications for gene transfer.

A D Miller 1
PMCID: PMC38070  PMID: 8876148

Abstract

Retroviruses can utilize a variety of cell-surface proteins for binding and entry into cells, and the cloning of several of these viral receptors has allowed refinement of models to explain retrovirus tropism. A single receptor appears to be necessary and sufficient for entry of many retroviruses, but exceptions to this simple model are accumulating. For example, HIV requires two proteins for cell entry, neither of which alone is sufficient; 10A1 murine leukemia virus can enter cells by using either of two distinct receptors; two retroviruses can use different receptors in some cells but use the same receptor for entry into other cells; and posttranslational protein modifications and secreted factors can dramatically influence virus entry. These findings greatly complicate the rules governing retrovirus tropism. The mechanism underlying retrovirus evolution to use many receptors for cell entry is not clear, although some evidence supports a mutational model for the evolution of new receptor specificities. Further study of factors that govern retrovirus entry into cells are important for achieving high-efficiency gene transduction to specific cells and for the design of retroviral vectors to target additional receptors for cell entry.

Full text

PDF
11407

Selected References

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

  1. Adamson M. C., Silver J., Kozak C. A. The mouse homolog of the Gibbon ape leukemia virus receptor: genetic mapping and a possible receptor function in rodents. Virology. 1991 Aug;183(2):778–781. doi: 10.1016/0042-6822(91)91010-e. [DOI] [PubMed] [Google Scholar]
  2. Albritton L. M., Kim J. W., Tseng L., Cunningham J. M. Envelope-binding domain in the cationic amino acid transporter determines the host range of ecotropic murine retroviruses. J Virol. 1993 Apr;67(4):2091–2096. doi: 10.1128/jvi.67.4.2091-2096.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Ban J., Portetelle D., Altaner C., Horion B., Milan D., Krchnak V., Burny A., Kettmann R. Isolation and characterization of a 2.3-kilobase-pair cDNA fragment encoding the binding domain of the bovine leukemia virus cell receptor. J Virol. 1993 Feb;67(2):1050–1057. doi: 10.1128/jvi.67.2.1050-1057.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ban J., Truong A. T., Horion B., Altaner C., Burny A., Portetelle D., Kettmann R. Isolation of the missing 5'-end of the encoding region of the bovine leukemia virus cell receptor gene. Arch Virol. 1994;138(3-4):379–383. doi: 10.1007/BF01379141. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Bates P., Young J. A., Varmus H. E. A receptor for subgroup A Rous sarcoma virus is related to the low density lipoprotein receptor. Cell. 1993 Sep 24;74(6):1043–1051. doi: 10.1016/0092-8674(93)90726-7. [DOI] [PubMed] [Google Scholar]
  8. Battini J. L., Heard J. M., Danos O. Receptor choice determinants in the envelope glycoproteins of amphotropic, xenotropic, and polytropic murine leukemia viruses. J Virol. 1992 Mar;66(3):1468–1475. doi: 10.1128/jvi.66.3.1468-1475.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bauer T. R., Jr, Miller A. D., Hickstein D. D. Improved transfer of the leukocyte integrin CD18 subunit into hematopoietic cell lines by using retroviral vectors having a gibbon ape leukemia virus envelope. Blood. 1995 Sep 15;86(6):2379–2387. [PubMed] [Google Scholar]
  10. Burns J. C., Friedmann T., Driever W., Burrascano M., Yee J. K. Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8033–8037. doi: 10.1073/pnas.90.17.8033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Chesebro B., Wehrly K. Different murine cell lines manifest unique patterns of interference to superinfection by murine leukemia viruses. Virology. 1985 Feb;141(1):119–129. doi: 10.1016/0042-6822(85)90188-6. [DOI] [PubMed] [Google Scholar]
  12. Dalgleish A. G., Beverley P. C., Clapham P. R., Crawford D. H., Greaves M. F., Weiss R. A. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984 Dec 20;312(5996):763–767. doi: 10.1038/312763a0. [DOI] [PubMed] [Google Scholar]
  13. Deng H., Liu R., Ellmeier W., Choe S., Unutmaz D., Burkhart M., Di Marzio P., Marmon S., Sutton R. E., Hill C. M. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun 20;381(6584):661–666. doi: 10.1038/381661a0. [DOI] [PubMed] [Google Scholar]
  14. Dragic T., Litwin V., Allaway G. P., Martin S. R., Huang Y., Nagashima K. A., Cayanan C., Maddon P. J., Koup R. A., Moore J. P. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996 Jun 20;381(6584):667–673. doi: 10.1038/381667a0. [DOI] [PubMed] [Google Scholar]
  15. Eiden M. V., Farrell K., Wilson C. A. Glycosylation-dependent inactivation of the ecotropic murine leukemia virus receptor. J Virol. 1994 Feb;68(2):626–631. doi: 10.1128/jvi.68.2.626-631.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Feng Y., Broder C. C., Kennedy P. E., Berger E. A. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science. 1996 May 10;272(5263):872–877. doi: 10.1126/science.272.5263.872. [DOI] [PubMed] [Google Scholar]
  17. Garcia J. V., Jones C., Miller A. D. Localization of the amphotropic murine leukemia virus receptor gene to the pericentromeric region of human chromosome 8. J Virol. 1991 Nov;65(11):6316–6319. doi: 10.1128/jvi.65.11.6316-6319.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gardner M. B., Kozak C. A., O'Brien S. J. The Lake Casitas wild mouse: evolving genetic resistance to retroviral disease. Trends Genet. 1991 Jan;7(1):22–27. doi: 10.1016/0168-9525(91)90017-k. [DOI] [PubMed] [Google Scholar]
  19. Gazdar A. F., Oie H., Lalley P., Moss W. W., Minna J. D. Identification of mouse chromosomes required for murine leukemia virus replication. Cell. 1977 Aug;11(4):949–956. doi: 10.1016/0092-8674(77)90306-3. [DOI] [PubMed] [Google Scholar]
  20. Halbert C. L., Alexander I. E., Wolgamot G. M., Miller A. D. Adeno-associated virus vectors transduce primary cells much less efficiently than immortalized cells. J Virol. 1995 Mar;69(3):1473–1479. doi: 10.1128/jvi.69.3.1473-1479.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hosie M. J., Willett B. J., Dunsford T. H., Jarrett O., Neil J. C. A monoclonal antibody which blocks infection with feline immunodeficiency virus identifies a possible non-CD4 receptor. J Virol. 1993 Mar;67(3):1667–1671. doi: 10.1128/jvi.67.3.1667-1671.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Isobe M., Huebner K., Maddon P. J., Littman D. R., Axel R., Croce C. M. The gene encoding the T-cell surface protein T4 is located on human chromosome 12. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4399–4402. doi: 10.1073/pnas.83.12.4399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kaelbling M., Eddy R., Shows T. B., Copeland N. G., Gilbert D. J., Jenkins N. A., Klinger H. P., O'Hara B. Localization of the human gene allowing infection by gibbon ape leukemia virus to human chromosome region 2q11-q14 and to the homologous region on mouse chromosome 2. J Virol. 1991 Apr;65(4):1743–1747. doi: 10.1128/jvi.65.4.1743-1747.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kasahara N., Dozy A. M., Kan Y. W. Tissue-specific targeting of retroviral vectors through ligand-receptor interactions. Science. 1994 Nov 25;266(5189):1373–1376. doi: 10.1126/science.7973726. [DOI] [PubMed] [Google Scholar]
  25. Kavanaugh M. P., Miller D. G., Zhang W., Law W., Kozak S. L., Kabat D., Miller A. D. Cell-surface receptors for gibbon ape leukemia virus and amphotropic murine retrovirus are inducible sodium-dependent phosphate symporters. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7071–7075. doi: 10.1073/pnas.91.15.7071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kewalramani V. N., Panganiban A. T., Emerman M. Spleen necrosis virus, an avian immunosuppressive retrovirus, shares a receptor with the type D simian retroviruses. J Virol. 1992 May;66(5):3026–3031. doi: 10.1128/jvi.66.5.3026-3031.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kim J. W., Closs E. I., Albritton L. M., Cunningham J. M. Transport of cationic amino acids by the mouse ecotropic retrovirus receptor. Nature. 1991 Aug 22;352(6337):725–728. doi: 10.1038/352725a0. [DOI] [PubMed] [Google Scholar]
  28. Klatzmann D., Champagne E., Chamaret S., Gruest J., Guetard D., Hercend T., Gluckman J. C., Montagnier L. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature. 1984 Dec 20;312(5996):767–768. doi: 10.1038/312767a0. [DOI] [PubMed] [Google Scholar]
  29. Kotin R. M., Berns K. I. Organization of adeno-associated virus DNA in latently infected Detroit 6 cells. Virology. 1989 Jun;170(2):460–467. doi: 10.1016/0042-6822(89)90437-6. [DOI] [PubMed] [Google Scholar]
  30. Miller A. D., Chen F. Retrovirus packaging cells based on 10A1 murine leukemia virus for production of vectors that use multiple receptors for cell entry. J Virol. 1996 Aug;70(8):5564–5571. doi: 10.1128/jvi.70.8.5564-5571.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Miller A. D., Miller D. G., Garcia J. V., Lynch C. M. Use of retroviral vectors for gene transfer and expression. Methods Enzymol. 1993;217:581–599. doi: 10.1016/0076-6879(93)17090-r. [DOI] [PubMed] [Google Scholar]
  32. Miller D. G., Adam M. A., Miller A. D. Gene transfer by retrovirus vectors occurs only in cells that are actively replicating at the time of infection. Mol Cell Biol. 1990 Aug;10(8):4239–4242. doi: 10.1128/mcb.10.8.4239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Miller D. G., Edwards R. H., Miller A. D. Cloning of the cellular receptor for amphotropic murine retroviruses reveals homology to that for gibbon ape leukemia virus. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):78–82. doi: 10.1073/pnas.91.1.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Miller D. G., Miller A. D. A family of retroviruses that utilize related phosphate transporters for cell entry. J Virol. 1994 Dec;68(12):8270–8276. doi: 10.1128/jvi.68.12.8270-8276.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Miller D. G., Miller A. D. Inhibitors of retrovirus infection are secreted by several hamster cell lines and are also present in hamster sera. J Virol. 1993 Sep;67(9):5346–5352. doi: 10.1128/jvi.67.9.5346-5352.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Miller D. G., Miller A. D. Tunicamycin treatment of CHO cells abrogates multiple blocks to retrovirus infection, one of which is due to a secreted inhibitor. J Virol. 1992 Jan;66(1):78–84. doi: 10.1128/jvi.66.1.78-84.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Naldini L., Blömer U., Gallay P., Ory D., Mulligan R., Gage F. H., Verma I. M., Trono D. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996 Apr 12;272(5259):263–267. doi: 10.1126/science.272.5259.263. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Ott D., Rein A. Basis for receptor specificity of nonecotropic murine leukemia virus surface glycoprotein gp70SU. J Virol. 1992 Aug;66(8):4632–4638. doi: 10.1128/jvi.66.8.4632-4638.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rein A., Schultz A. M., Bader J. P., Bassin R. H. Inhibitors of glycosylation reverse retroviral interference. Virology. 1982 May;119(1):185–192. doi: 10.1016/0042-6822(82)90075-7. [DOI] [PubMed] [Google Scholar]
  41. Robinson H. L., Astrin S. M., Senior A. M., Salazar F. H. Host Susceptibility to endogenous viruses: defective, glycoprotein-expressing proviruses interfere with infections. J Virol. 1981 Dec;40(3):745–751. doi: 10.1128/jvi.40.3.745-751.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Sattentau Q. J., Clapham P. R., Weiss R. A., Beverley P. C., Montagnier L., Alhalabi M. F., Gluckmann J. C., Klatzmann D. The human and simian immunodeficiency viruses HIV-1, HIV-2 and SIV interact with similar epitopes on their cellular receptor, the CD4 molecule. AIDS. 1988 Apr;2(2):101–105. doi: 10.1097/00002030-198804000-00005. [DOI] [PubMed] [Google Scholar]
  43. Somia N. V., Zoppé M., Verma I. M. Generation of targeted retroviral vectors by using single-chain variable fragment: an approach to in vivo gene delivery. Proc Natl Acad Sci U S A. 1995 Aug 1;92(16):7570–7574. doi: 10.1073/pnas.92.16.7570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sommerfelt M. A., Weiss R. A. Receptor interference groups of 20 retroviruses plating on human cells. Virology. 1990 May;176(1):58–69. doi: 10.1016/0042-6822(90)90230-o. [DOI] [PubMed] [Google Scholar]
  45. Sommerfelt M. A., Williams B. P., Clapham P. R., Solomon E., Goodfellow P. N., Weiss R. A. Human T cell leukemia viruses use a receptor determined by human chromosome 17. Science. 1988 Dec 16;242(4885):1557–1559. doi: 10.1126/science.3201246. [DOI] [PubMed] [Google Scholar]
  46. Sommerfelt M. A., Williams B. P., McKnight A., Goodfellow P. N., Weiss R. A. Localization of the receptor gene for type D simian retroviruses on human chromosome 19. J Virol. 1990 Dec;64(12):6214–6220. doi: 10.1128/jvi.64.12.6214-6220.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wang H., Kavanaugh M. P., North R. A., Kabat D. Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter. Nature. 1991 Aug 22;352(6337):729–731. doi: 10.1038/352729a0. [DOI] [PubMed] [Google Scholar]
  48. Willett B. J., Hosie M. J., Jarrett O., Neil J. C. Identification of a putative cellular receptor for feline immunodeficiency virus as the feline homologue of CD9. Immunology. 1994 Feb;81(2):228–233. [PMC free article] [PubMed] [Google Scholar]
  49. Wilson C. A., Farrell K. B., Eiden M. V. Properties of a unique form of the murine amphotropic leukemia virus receptor expressed on hamster cells. J Virol. 1994 Dec;68(12):7697–7703. doi: 10.1128/jvi.68.12.7697-7703.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Yoshimoto T., Yoshimoto E., Meruelo D. Identification of amino acid residues critical for infection with ecotropic murine leukemia retrovirus. J Virol. 1993 Mar;67(3):1310–1314. doi: 10.1128/jvi.67.3.1310-1314.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. van Zeijl M., Johann S. V., Closs E., Cunningham J., Eddy R., Shows T. B., O'Hara B. A human amphotropic retrovirus receptor is a second member of the gibbon ape leukemia virus receptor family. Proc Natl Acad Sci U S A. 1994 Feb 1;91(3):1168–1172. doi: 10.1073/pnas.91.3.1168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. von Kalle C., Kiem H. P., Goehle S., Darovsky B., Heimfeld S., Torok-Storb B., Storb R., Schuening F. G. Increased gene transfer into human hematopoietic progenitor cells by extended in vitro exposure to a pseudotyped retroviral vector. Blood. 1994 Nov 1;84(9):2890–2897. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES