Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1988 Sep 1;107(3):959–968. doi: 10.1083/jcb.107.3.959

Human immunodeficiency virus infection of T cells and monocytes proceeds via receptor-mediated endocytosis

PMCID: PMC2115279  PMID: 3262112

Abstract

The rates of internalization and uncoating of 32P-labelled human immunodeficiency virus (HIV) in the human T lymphoid cell line CEM are consonant with a receptor-mediated endocytosis mechanism of entry. This interpretation was affirmed by electron microscopic observation of virions within endosomes. Virus binding and infectivity were inhibited to the same extent by pretreatment with OKT4A antibody, therefore, the CD4 receptor-dependent pathway of internalization appears to be the infectious route of entry. The pattern of internalization by the human monoblastoid cell line U937 proved to be more complex, involving rapid and efficient CD4-independent internalization. Electron microscopy revealed the presence of large intracellular vesicles, each containing several virions. Antibody against the CD4 receptor for virus efficiently blocked infection, but did not reduce significantly HIV binding or internalization in the U937 cell line. Consequently, U937 cells have a CD4-independent pathway of virus internalization that does not coincide with the route of entry for infectious HIV.

Full Text

The Full Text of this article is available as a PDF (2.9 MB).

Selected References

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

  1. Aloia R. C., Jensen F. C., Curtain C. C., Mobley P. W., Gordon L. M. Lipid composition and fluidity of the human immunodeficiency virus. Proc Natl Acad Sci U S A. 1988 Feb;85(3):900–904. doi: 10.1073/pnas.85.3.900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Andersen K. B., Nexø B. A. Entry of murine retrovirus into mouse fibroblasts. Virology. 1983 Feb;125(1):85–98. doi: 10.1016/0042-6822(83)90065-x. [DOI] [PubMed] [Google Scholar]
  3. Bleil J. D., Bretscher M. S. Transferrin receptor and its recycling in HeLa cells. EMBO J. 1982;1(3):351–355. doi: 10.1002/j.1460-2075.1982.tb01173.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chany-Fournier F., Chany C., Lafay F. Mechanism of polykaryocyte induction by vesicular stomatitis virus in rat XC cells. J Gen Virol. 1977 Feb;34(2):305–314. doi: 10.1099/0022-1317-34-2-305. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Gartner S., Markovits P., Markovitz D. M., Kaplan M. H., Gallo R. C., Popovic M. The role of mononuclear phagocytes in HTLV-III/LAV infection. Science. 1986 Jul 11;233(4760):215–219. doi: 10.1126/science.3014648. [DOI] [PubMed] [Google Scholar]
  7. Gollins S. W., Porterfield J. S. A new mechanism for the neutralization of enveloped viruses by antiviral antibody. Nature. 1986 May 15;321(6067):244–246. doi: 10.1038/321244a0. [DOI] [PubMed] [Google Scholar]
  8. Gollins S. W., Porterfield J. S. Flavivirus infection enhancement in macrophages: an electron microscopic study of viral cellular entry. J Gen Virol. 1985 Sep;66(Pt 9):1969–1982. doi: 10.1099/0022-1317-66-9-1969. [DOI] [PubMed] [Google Scholar]
  9. Gollins S. W., Porterfield J. S. Flavivirus infection enhancement in macrophages: radioactive and biological studies on the effect of antibody on viral fate. J Gen Virol. 1984 Aug;65(Pt 8):1261–1272. doi: 10.1099/0022-1317-65-8-1261. [DOI] [PubMed] [Google Scholar]
  10. Helenius A., Marsh M., White J. Inhibition of Semliki forest virus penetration by lysosomotropic weak bases. J Gen Virol. 1982 Jan;58(Pt 1):47–61. doi: 10.1099/0022-1317-58-1-47. [DOI] [PubMed] [Google Scholar]
  11. Hirsch J. G., Fedorko M. E. Ultrastructure of human leukocytes after simultaneous fixation with glutaraldehyde and osmium tetroxide and "postfixation" in uranyl acetate. J Cell Biol. 1968 Sep;38(3):615–627. doi: 10.1083/jcb.38.3.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ho D. D., Rota T. R., Hirsch M. S. Infection of monocyte/macrophages by human T lymphotropic virus type III. J Clin Invest. 1986 May;77(5):1712–1715. doi: 10.1172/JCI112491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hoxie J. A., Flaherty L. E., Haggarty B. S., Rackowski J. L. Infection of T4 lymphocytes by HTLV-III does not require expression of the OKT4 epitope. J Immunol. 1986 Jan;136(2):361–363. [PubMed] [Google Scholar]
  14. Inaba K., Steinman R. M. Monoclonal antibodies to LFA-1 and to CD4 inhibit the mixed leukocyte reaction after the antigen-dependent clustering of dendritic cells and T lymphocytes. J Exp Med. 1987 May 1;165(5):1403–1417. doi: 10.1084/jem.165.5.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kennedy-Stoskopf S., Narayan O. Neutralizing antibodies to visna lentivirus: mechanism of action and possible role in virus persistence. J Virol. 1986 Jul;59(1):37–44. doi: 10.1128/jvi.59.1.37-44.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klatzmann D., Barré-Sinoussi F., Nugeyre M. T., Danquet C., Vilmer E., Griscelli C., Brun-Veziret F., Rouzioux C., Gluckman J. C., Chermann J. C. Selective tropism of lymphadenopathy associated virus (LAV) for helper-inducer T lymphocytes. Science. 1984 Jul 6;225(4657):59–63. doi: 10.1126/science.6328660. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. Marsh M. The entry of enveloped viruses into cells by endocytosis. Biochem J. 1984 Feb 15;218(1):1–10. doi: 10.1042/bj2180001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Matlin K. S., Reggio H., Helenius A., Simons K. Infectious entry pathway of influenza virus in a canine kidney cell line. J Cell Biol. 1981 Dec;91(3 Pt 1):601–613. doi: 10.1083/jcb.91.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Matlin K. S., Reggio H., Helenius A., Simons K. Pathway of vesicular stomatitis virus entry leading to infection. J Mol Biol. 1982 Apr 15;156(3):609–631. doi: 10.1016/0022-2836(82)90269-8. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Nicholson J. K., Cross G. D., Callaway C. S., McDougal J. S. In vitro infection of human monocytes with human T lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). J Immunol. 1986 Jul 1;137(1):323–329. [PubMed] [Google Scholar]
  24. Nishiyama Y., Ito Y., Shimokata K., Kimura Y., Nagata I. Polykaryocyte formation induced by VSV in mouse L cells. J Gen Virol. 1976 Jul;32(1):85–96. doi: 10.1099/0022-1317-32-1-85. [DOI] [PubMed] [Google Scholar]
  25. Okada Y., Koseki I., Kim J., Maeda Y., Hashimoto T. Modification of cell membranes with viral envelopes during fusion of cells with HVJ (Sendai virus). Exp Cell Res. 1975 Jul;93(2):368–378. doi: 10.1016/0014-4827(75)90462-0. [DOI] [PubMed] [Google Scholar]
  26. Pauza C. D., Bleil J. D., Lennox E. S. The control of transferrin receptor synthesis in mitogen-stimulated human lymphocytes. Exp Cell Res. 1984 Oct;154(2):510–520. doi: 10.1016/0014-4827(84)90175-7. [DOI] [PubMed] [Google Scholar]
  27. Popovic M., Sarngadharan M. G., Read E., Gallo R. C. Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science. 1984 May 4;224(4648):497–500. doi: 10.1126/science.6200935. [DOI] [PubMed] [Google Scholar]
  28. Rivas A., Takada S., Koide J., Sonderstrup-McDevitt G., Engleman E. G. CD4 molecules are associated with the antigen receptor complex on activated but not resting T cells. J Immunol. 1988 May 1;140(9):2912–2918. [PubMed] [Google Scholar]
  29. 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]
  30. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  31. Weyand C. M., Goronzy J., Fathman C. G. Modulation of CD4 by antigenic activation. J Immunol. 1987 Mar 1;138(5):1351–1354. [PubMed] [Google Scholar]
  32. White J., Helenius A. pH-dependent fusion between the Semliki Forest virus membrane and liposomes. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3273–3277. doi: 10.1073/pnas.77.6.3273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. White J., Matlin K., Helenius A. Cell fusion by Semliki Forest, influenza, and vesicular stomatitis viruses. J Cell Biol. 1981 Jun;89(3):674–679. doi: 10.1083/jcb.89.3.674. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES