Abstract
Two primary cell targets for human immunodeficiency virus type 1 (HIV-1) infection in vivo are CD4+ T lymphocytes and monocyte-derived macrophages (MDM). HIV-1 encodes envelope glycoproteins which mediate virus entry into these cells. We have utilized infected and radiolabelled primary peripheral blood mononuclear cell (PBMC) and MDM cultures to examine the biochemical and antigenic properties of the HIV-1 envelope produced in these two cell types. The gp120 produced in MDM migrates as a broad, diffuse band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels compared with that of the more homogeneous gp120 released from PBMCs. Glycosidase analyses indicated that the diffuse appearance of the MDM gp120 is due to the presence of asparagine-linked carbohydrates containing lactosaminoglycans, a modification not observed with the gp120 produced in PBMCs. Neutralization experiments, using isogeneic PBMC and MDM-derived macrophage-tropic HIV-1 isolates, indicate that 8- to 10-fold more neutralizing antibody, directed against the viral envelope, is required to block virus produced from MDM. These results demonstrate that HIV-1 released from infected PBMC and MDM cultures differs in its biochemical and antigenic properties.
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- Allan J. S., Coligan J. E., Barin F., McLane M. F., Sodroski J. G., Rosen C. A., Haseltine W. A., Lee T. H., Essex M. Major glycoprotein antigens that induce antibodies in AIDS patients are encoded by HTLV-III. Science. 1985 May 31;228(4703):1091–1094. doi: 10.1126/science.2986290. [DOI] [PubMed] [Google Scholar]
- Arthur L. O., Bess J. W., Jr, Sowder R. C., 2nd, Benveniste R. E., Mann D. L., Chermann J. C., Henderson L. E. Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines. Science. 1992 Dec 18;258(5090):1935–1938. doi: 10.1126/science.1470916. [DOI] [PubMed] [Google Scholar]
- Back N. K., Smit L., De Jong J. J., Keulen W., Schutten M., Goudsmit J., Tersmette M. An N-glycan within the human immunodeficiency virus type 1 gp120 V3 loop affects virus neutralization. Virology. 1994 Mar;199(2):431–438. doi: 10.1006/viro.1994.1141. [DOI] [PubMed] [Google Scholar]
- Bolmstedt A., Olofsson S., Sjögren-Jansson E., Jeansson S., Sjöblom I., Akerblom L., Hansen J. E., Hu S. L. Carbohydrate determinant NeuAc-Gal beta (1-4) of N-linked glycans modulates the antigenic activity of human immunodeficiency virus type 1 glycoprotein gp120. J Gen Virol. 1992 Dec;73(Pt 12):3099–3105. doi: 10.1099/0022-1317-73-12-3099. [DOI] [PubMed] [Google Scholar]
- Cheng-Mayer C., Quiroga M., Tung J. W., Dina D., Levy J. A. Viral determinants of human immunodeficiency virus type 1 T-cell or macrophage tropism, cytopathogenicity, and CD4 antigen modulation. J Virol. 1990 Sep;64(9):4390–4398. doi: 10.1128/jvi.64.9.4390-4398.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheng-Mayer C., Seto D., Tateno M., Levy J. A. Biologic features of HIV-1 that correlate with virulence in the host. Science. 1988 Apr 1;240(4848):80–82. doi: 10.1126/science.2832945. [DOI] [PubMed] [Google Scholar]
- Chesebro B., Nishio J., Perryman S., Cann A., O'Brien W., Chen I. S., Wehrly K. Identification of human immunodeficiency virus envelope gene sequences influencing viral entry into CD4-positive HeLa cells, T-leukemia cells, and macrophages. J Virol. 1991 Nov;65(11):5782–5789. doi: 10.1128/jvi.65.11.5782-5789.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Davis D., Stephens D. M., Willers C., Lachmann P. J. Glycosylation governs the binding of antipeptide antibodies to regions of hypervariable amino acid sequence within recombinant gp120 of human immunodeficiency virus type 1. J Gen Virol. 1990 Dec;71(Pt 12):2889–2898. doi: 10.1099/0022-1317-71-12-2889. [DOI] [PubMed] [Google Scholar]
- Fauci A. S. The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science. 1988 Feb 5;239(4840):617–622. doi: 10.1126/science.3277274. [DOI] [PubMed] [Google Scholar]
- Fenouillet E., Gluckman J. C., Bahraoui E. Role of N-linked glycans of envelope glycoproteins in infectivity of human immunodeficiency virus type 1. J Virol. 1990 Jun;64(6):2841–2848. doi: 10.1128/jvi.64.6.2841-2848.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Freed E. O., Myers D. J., Risser R. Characterization of the fusion domain of the human immunodeficiency virus type 1 envelope glycoprotein gp41. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4650–4654. doi: 10.1073/pnas.87.12.4650. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fukuda M. N., Matsumura G. Endo-beta-galactosidase of Escherichia freundii. Purification and endoglycosidic action on keratan sulfates, oligosaccharides, and blood group active glycoprotein. J Biol Chem. 1976 Oct 25;251(20):6218–6225. [PubMed] [Google Scholar]
- Fukuda M., Dell A., Oates J. E., Fukuda M. N. Structure of branched lactosaminoglycan, the carbohydrate moiety of band 3 isolated from adult human erythrocytes. J Biol Chem. 1984 Jul 10;259(13):8260–8273. [PubMed] [Google Scholar]
- Fukuda M., Koeffler H. P., Minowada J. Membrane differentiation in human myeloid cells: expression of unique profiles of cell surface glycoproteins in myeloid leukemic cell lines blocked at different stages of differentiation and maturation. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6299–6303. doi: 10.1073/pnas.78.10.6299. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Gelderblom H. R., Hausmann E. H., Ozel M., Pauli G., Koch M. A. Fine structure of human immunodeficiency virus (HIV) and immunolocalization of structural proteins. Virology. 1987 Jan;156(1):171–176. doi: 10.1016/0042-6822(87)90449-1. [DOI] [PubMed] [Google Scholar]
- Gendelman H. E., Orenstein J. M., Martin M. A., Ferrua C., Mitra R., Phipps T., Wahl L. A., Lane H. C., Fauci A. S., Burke D. S. Efficient isolation and propagation of human immunodeficiency virus on recombinant colony-stimulating factor 1-treated monocytes. J Exp Med. 1988 Apr 1;167(4):1428–1441. doi: 10.1084/jem.167.4.1428. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gerrard T. L., Jurgensen C. H., Fauci A. S. Differential effect of monoclonal anti-DR antibody on monocytes in antigen- and mitogen-stimulated responses: mechanism of inhibition and relationship to interleukin 1 secretion. Cell Immunol. 1983 Dec;82(2):394–402. doi: 10.1016/0008-8749(83)90172-7. [DOI] [PubMed] [Google Scholar]
- Geyer H., Holschbach C., Hunsmann G., Schneider J. Carbohydrates of human immunodeficiency virus. Structures of oligosaccharides linked to the envelope glycoprotein 120. J Biol Chem. 1988 Aug 25;263(24):11760–11767. [PubMed] [Google Scholar]
- Gram G. J., Hemming A., Bolmstedt A., Jansson B., Olofsson S., Akerblom L., Nielsen J. O., Hansen J. E. Identification of an N-linked glycan in the V1-loop of HIV-1 gp120 influencing neutralization by anti-V3 antibodies and soluble CD4. Arch Virol. 1994;139(3-4):253–261. doi: 10.1007/BF01310789. [DOI] [PubMed] [Google Scholar]
- Hansen J. E., Clausen H., Nielsen C., Teglbjaerg L. S., Hansen L. L., Nielsen C. M., Dabelsteen E., Mathiesen L., Hakomori S. I., Nielsen J. O. Inhibition of human immunodeficiency virus (HIV) infection in vitro by anticarbohydrate monoclonal antibodies: peripheral glycosylation of HIV envelope glycoprotein gp120 may be a target for virus neutralization. J Virol. 1990 Jun;64(6):2833–2840. doi: 10.1128/jvi.64.6.2833-2840.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kowalski M., Potz J., Basiripour L., Dorfman T., Goh W. C., Terwilliger E., Dayton A., Rosen C., Haseltine W., Sodroski J. Functional regions of the envelope glycoprotein of human immunodeficiency virus type 1. Science. 1987 Sep 11;237(4820):1351–1355. doi: 10.1126/science.3629244. [DOI] [PubMed] [Google Scholar]
- Koyanagi Y., Miles S., Mitsuyasu R. T., Merrill J. E., Vinters H. V., Chen I. S. Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms. Science. 1987 May 15;236(4803):819–822. doi: 10.1126/science.3646751. [DOI] [PubMed] [Google Scholar]
- Lazdins J. K., Woods-Cook K., Walker M., Alteri E. The lipophilic muramyl peptide MTP-PE is a potent inhibitor of HIV replication in macrophages. AIDS Res Hum Retroviruses. 1990 Oct;6(10):1157–1161. doi: 10.1089/aid.1990.6.1157. [DOI] [PubMed] [Google Scholar]
- Levy J. A. Pathogenesis of human immunodeficiency virus infection. Microbiol Rev. 1993 Mar;57(1):183–289. doi: 10.1128/mr.57.1.183-289.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- McKeating J. A., McKnight A., Moore J. P. Differential loss of envelope glycoprotein gp120 from virions of human immunodeficiency virus type 1 isolates: effects on infectivity and neutralization. J Virol. 1991 Feb;65(2):852–860. doi: 10.1128/jvi.65.2.852-860.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Brien W. A., Koyanagi Y., Namazie A., Zhao J. Q., Diagne A., Idler K., Zack J. A., Chen I. S. HIV-1 tropism for mononuclear phagocytes can be determined by regions of gp120 outside the CD4-binding domain. Nature. 1990 Nov 1;348(6296):69–73. doi: 10.1038/348069a0. [DOI] [PubMed] [Google Scholar]
- Plaas A. H., Wong-Palms S. Biosynthetic mechanisms for the addition of polylactosamine to chondrocyte fibromodulin. J Biol Chem. 1993 Dec 15;268(35):26634–26644. [PubMed] [Google Scholar]
- Potts B. J., Maury W., Martin M. A. Replication of HIV-1 in primary monocyte cultures. Virology. 1990 Apr;175(2):465–476. doi: 10.1016/0042-6822(90)90431-p. [DOI] [PubMed] [Google Scholar]
- Prince A. M., Reesink H., Pascual D., Horowitz B., Hewlett I., Murthy K. K., Cobb K. E., Eichberg J. W. Prevention of HIV infection by passive immunization with HIV immunoglobulin. AIDS Res Hum Retroviruses. 1991 Dec;7(12):971–973. doi: 10.1089/aid.1991.7.971. [DOI] [PubMed] [Google Scholar]
- Rademacher T. W., Parekh R. B., Dwek R. A. Glycobiology. Annu Rev Biochem. 1988;57:785–838. doi: 10.1146/annurev.bi.57.070188.004033. [DOI] [PubMed] [Google Scholar]
- Schneider J., Kaaden O., Copeland T. D., Oroszlan S., Hunsmann G. Shedding and interspecies type sero-reactivity of the envelope glycopolypeptide gp120 of the human immunodeficiency virus. J Gen Virol. 1986 Nov;67(Pt 11):2533–2538. doi: 10.1099/0022-1317-67-11-2533. [DOI] [PubMed] [Google Scholar]
- Shibata R., Hoggan M. D., Broscius C., Englund G., Theodore T. S., Buckler-White A., Arthur L. O., Israel Z., Schultz A., Lane H. C. Isolation and characterization of a syncytium-inducing, macrophage/T-cell line-tropic human immunodeficiency virus type 1 isolate that readily infects chimpanzee cells in vitro and in vivo. J Virol. 1995 Jul;69(7):4453–4462. doi: 10.1128/jvi.69.7.4453-4462.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shioda T., Levy J. A., Cheng-Mayer C. Macrophage and T cell-line tropisms of HIV-1 are determined by specific regions of the envelope gp120 gene. Nature. 1991 Jan 10;349(6305):167–169. doi: 10.1038/349167a0. [DOI] [PubMed] [Google Scholar]
- Stein B. S., Engleman E. G. Intracellular processing of the gp160 HIV-1 envelope precursor. Endoproteolytic cleavage occurs in a cis or medial compartment of the Golgi complex. J Biol Chem. 1990 Feb 15;265(5):2640–2649. [PubMed] [Google Scholar]
- 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]
- Tarentino A. L., Quinones G., Trumble A., Changchien L. M., Duceman B., Maley F., Plummer T. H., Jr Molecular cloning and amino acid sequence of peptide-N4-(N-acetyl-beta-D-glucosaminyl)asparagine amidase from flavobacterium meningosepticum. J Biol Chem. 1990 Apr 25;265(12):6961–6966. [PubMed] [Google Scholar]
- Theodore T. S., Englund G., Buckler-White A., Buckler C. E., Martin M. A., Peden K. W. Construction and characterization of a stable full-length macrophage-tropic HIV type 1 molecular clone that directs the production of high titers of progeny virions. AIDS Res Hum Retroviruses. 1996 Feb 10;12(3):191–194. doi: 10.1089/aid.1996.12.191. [DOI] [PubMed] [Google Scholar]
- Warrier S. V., Pinter A., Honnen W. J., Girard M., Muchmore E., Tilley S. A. A novel, glycan-dependent epitope in the V2 domain of human immunodeficiency virus type 1 gp120 is recognized by a highly potent, neutralizing chimpanzee monoclonal antibody. J Virol. 1994 Jul;68(7):4636–4642. doi: 10.1128/jvi.68.7.4636-4642.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Westervelt P., Gendelman H. E., Ratner L. Identification of a determinant within the human immunodeficiency virus 1 surface envelope glycoprotein critical for productive infection of primary monocytes. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3097–3101. doi: 10.1073/pnas.88.8.3097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willey R. L., Bonifacino J. S., Potts B. J., Martin M. A., Klausner R. D. Biosynthesis, cleavage, and degradation of the human immunodeficiency virus 1 envelope glycoprotein gp160. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9580–9584. doi: 10.1073/pnas.85.24.9580. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willey R. L., Klimkait T., Frucht D. M., Bonifacino J. S., Martin M. A. Mutations within the human immunodeficiency virus type 1 gp160 envelope glycoprotein alter its intracellular transport and processing. Virology. 1991 Sep;184(1):319–329. doi: 10.1016/0042-6822(91)90848-6. [DOI] [PubMed] [Google Scholar]
- Willey R. L., Martin M. A., Peden K. W. Increase in soluble CD4 binding to and CD4-induced dissociation of gp120 from virions correlates with infectivity of human immunodeficiency virus type 1. J Virol. 1994 Feb;68(2):1029–1039. doi: 10.1128/jvi.68.2.1029-1039.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willey R. L., Smith D. H., Lasky L. A., Theodore T. S., Earl P. L., Moss B., Capon D. J., Martin M. A. In vitro mutagenesis identifies a region within the envelope gene of the human immunodeficiency virus that is critical for infectivity. J Virol. 1988 Jan;62(1):139–147. doi: 10.1128/jvi.62.1.139-147.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Willey R. L., Theodore T. S., Martin M. A. Amino acid substitutions in the human immunodeficiency virus type 1 gp120 V3 loop that change viral tropism also alter physical and functional properties of the virion envelope. J Virol. 1994 Jul;68(7):4409–4419. doi: 10.1128/jvi.68.7.4409-4419.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams M. A., Lamb R. A. Polylactosaminoglycan modification of a small integral membrane glycoprotein, influenza B virus NB. Mol Cell Biol. 1988 Mar;8(3):1186–1196. doi: 10.1128/mcb.8.3.1186. [DOI] [PMC free article] [PubMed] [Google Scholar]
