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. 1995 Aug 1;182(2):501–509. doi: 10.1084/jem.182.2.501

Role of virion-associated glycosylphosphatidylinositol-linked proteins CD55 and CD59 in complement resistance of cell line-derived and primary isolates of HIV-1

PMCID: PMC2192116  PMID: 7543140

Abstract

This study investigates whether cell-derived glycosylphosphatidylinositol-linked complement control proteins CD55 and CD59 can be incorporated into HIV-1 virions and contribute to complement resistance. Virus was prepared by transfection of cell lines with pNL4-3, and primary isolates of HIV-1 were derived from patients' PBMCs. Virus was tested for sensitivity to complement-mediated virolysis in the presence of anti-gp160 antibody. Viral preparations from JY33 cells, which lack CD55 and CD59, were highly sensitive to complement. HIV-1 preparations from H9 and U937 cells, which express low levels of CD55 and CD59, had intermediate to high sensitivity while other cell line-derived viruses and primary isolates of HIV-1 were resistant to complement-mediated virolysis. Although the primary isolates were not lysed, they activated complement as measured by binding to a complement receptor positive cell line. While the primary isolates were resistant to lysis in the presence of HIV-specific antibody, antibody to CD59 induced lysis. Likewise, antibody to CD55 and CD59 induced lysis of cell line-derived virus. Western blot analysis of purified virus showed bands corresponding to CD55 and CD59. Phosphatidylinositol-specific phospholipase C treatment of either cell line-derived or primary isolates of HIV-1 increased sensitivity to complement while incubation of sensitive virus with purified CD55 and CD59 increased resistance to complement. These results show that CD55 and CD59 are incorporated into HIV-1 particles and function to protect virions from complement-mediated destruction, and they are the first report of host cell proteins functioning in protection of HIV-1 from immune effector mechanisms.

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Selected References

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  1. Adachi A., Gendelman H. E., Koenig S., Folks T., Willey R., Rabson A., Martin M. A. Production of acquired immunodeficiency syndrome-associated retrovirus in human and nonhuman cells transfected with an infectious molecular clone. J Virol. 1986 Aug;59(2):284–291. doi: 10.1128/jvi.59.2.284-291.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. 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]
  3. Banapour B., Sernatinger J., Levy J. A. The AIDS-associated retrovirus is not sensitive to lysis or inactivation by human serum. Virology. 1986 Jul 15;152(1):268–271. doi: 10.1016/0042-6822(86)90392-2. [DOI] [PubMed] [Google Scholar]
  4. Bartholomew R. M., Esser A. F., Müller-Eberhard H. J. Lysis of oncornaviruses by human serum. Isolation of the viral complement (C1) receptor and identification as p15E. J Exp Med. 1978 Mar 1;147(3):844–853. doi: 10.1084/jem.147.3.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Benkirane M., Blanc-Zouaoui D., Hirn M., Devaux C. Involvement of human leukocyte antigen class I molecules in human immunodeficiency virus infection of CD4-positive cells. J Virol. 1994 Oct;68(10):6332–6339. doi: 10.1128/jvi.68.10.6332-6339.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Boyer V., Desgranges C., Trabaud M. A., Fischer E., Kazatchkine M. D. Complement mediates human immunodeficiency virus type 1 infection of a human T cell line in a CD4- and antibody-independent fashion. J Exp Med. 1991 May 1;173(5):1151–1158. doi: 10.1084/jem.173.5.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chaffee S., Leeds J. M., Matthews T. J., Weinhold K. J., Skinner M., Bolognesi D. P., Hershfield M. S. Phenotypic variation in the response to the human immunodeficiency virus among derivatives of the CEM T and WIL-2 B cell lines. J Exp Med. 1988 Aug 1;168(2):605–621. doi: 10.1084/jem.168.2.605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cooper N. R., Jensen F. C., Welsh R. M., Jr, Oldstone M. B. Lysis of RNA tumor viruses by human serum: direct antibody-independent triggering of the classical complement pathway. J Exp Med. 1976 Oct 1;144(4):970–984. doi: 10.1084/jem.144.4.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davitz M. A., Low M. G., Nussenzweig V. Release of decay-accelerating factor (DAF) from the cell membrane by phosphatidylinositol-specific phospholipase C (PIPLC). Selective modification of a complement regulatory protein. J Exp Med. 1986 May 1;163(5):1150–1161. doi: 10.1084/jem.163.5.1150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Delibrias C. C., Kazatchkine M. D., Fischer E. Evidence for the role of CR1 (CD35), in addition to CR2 (CD21), in facilitating infection of human T cells with opsonized HIV. Scand J Immunol. 1993 Aug;38(2):183–189. doi: 10.1111/j.1365-3083.1993.tb01711.x. [DOI] [PubMed] [Google Scholar]
  11. Ferguson M. A., Williams A. F. Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures. Annu Rev Biochem. 1988;57:285–320. doi: 10.1146/annurev.bi.57.070188.001441. [DOI] [PubMed] [Google Scholar]
  12. Ho D. D., Neumann A. U., Perelson A. S., Chen W., Leonard J. M., Markowitz M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature. 1995 Jan 12;373(6510):123–126. doi: 10.1038/373123a0. [DOI] [PubMed] [Google Scholar]
  13. Holguin M. H., Fredrick L. R., Bernshaw N. J., Wilcox L. A., Parker C. J. Isolation and characterization of a membrane protein from normal human erythrocytes that inhibits reactive lysis of the erythrocytes of paroxysmal nocturnal hemoglobinuria. J Clin Invest. 1989 Jul;84(1):7–17. doi: 10.1172/JCI114172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hoshino H., Tanaka H., Miwa M., Okada H. Human T-cell leukaemia virus is not lysed by human serum. 1984 Jul 26-Aug 1Nature. 310(5975):324–325. doi: 10.1038/310324a0. [DOI] [PubMed] [Google Scholar]
  15. Hourcade D., Holers V. M., Atkinson J. P. The regulators of complement activation (RCA) gene cluster. Adv Immunol. 1989;45:381–416. doi: 10.1016/s0065-2776(08)60697-5. [DOI] [PubMed] [Google Scholar]
  16. June R. A., Schade S. Z., Bankowski M. J., Kuhns M., McNamara A., Lint T. F., Landay A. L., Spear G. T. Complement and antibody mediate enhancement of HIV infection by increasing virus binding and provirus formation. AIDS. 1991 Mar;5(3):269–274. doi: 10.1097/00002030-199103000-00004. [DOI] [PubMed] [Google Scholar]
  17. Lachmann P. J. The control of homologous lysis. Immunol Today. 1991 Sep;12(9):312–315. doi: 10.1016/0167-5699(91)90005-E. [DOI] [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. Lopata M. A., Cleveland D. W., Sollner-Webb B. High level transient expression of a chloramphenicol acetyl transferase gene by DEAE-dextran mediated DNA transfection coupled with a dimethyl sulfoxide or glycerol shock treatment. Nucleic Acids Res. 1984 Jul 25;12(14):5707–5717. doi: 10.1093/nar/12.14.5707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lublin D. M., Atkinson J. P. Decay-accelerating factor: biochemistry, molecular biology, and function. Annu Rev Immunol. 1989;7:35–58. doi: 10.1146/annurev.iy.07.040189.000343. [DOI] [PubMed] [Google Scholar]
  21. McKeating J. A., Griffiths P. D., Grundy J. E. Cytomegalovirus in urine specimens has host beta 2 microglobulin bound to the viral envelope: a mechanism of evading the host immune response? J Gen Virol. 1987 Mar;68(Pt 3):785–792. doi: 10.1099/0022-1317-68-3-785. [DOI] [PubMed] [Google Scholar]
  22. Medof M. E., Kinoshita T., Silber R., Nussenzweig V. Amelioration of lytic abnormalities of paroxysmal nocturnal hemoglobinuria with decay-accelerating factor. Proc Natl Acad Sci U S A. 1985 May;82(9):2980–2984. doi: 10.1073/pnas.82.9.2980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Meerloo T., Sheikh M. A., Bloem A. C., de Ronde A., Schutten M., van Els C. A., Roholl P. J., Joling P., Goudsmit J., Schuurman H. J. Host cell membrane proteins on human immunodeficiency virus type 1 after in vitro infection of H9 cells and blood mononuclear cells. An immuno-electron microscopic study. J Gen Virol. 1993 Jan;74(Pt 1):129–135. doi: 10.1099/0022-1317-74-1-129. [DOI] [PubMed] [Google Scholar]
  24. Meri S., Morgan B. P., Davies A., Daniels R. H., Olavesen M. G., Waldmann H., Lachmann P. J. Human protectin (CD59), an 18,000-20,000 MW complement lysis restricting factor, inhibits C5b-8 catalysed insertion of C9 into lipid bilayers. Immunology. 1990 Sep;71(1):1–9. [PMC free article] [PubMed] [Google Scholar]
  25. Orentas R. J., Hildreth J. E. Association of host cell surface adhesion receptors and other membrane proteins with HIV and SIV. AIDS Res Hum Retroviruses. 1993 Nov;9(11):1157–1165. doi: 10.1089/aid.1993.9.1157. [DOI] [PubMed] [Google Scholar]
  26. Pantaleo G., Butini L., Graziosi C., Poli G., Schnittman S. M., Greenhouse J. J., Gallin J. I., Fauci A. S. Human immunodeficiency virus (HIV) infection in CD4+ T lymphocytes genetically deficient in LFA-1: LFA-1 is required for HIV-mediated cell fusion but not for viral transmission. J Exp Med. 1991 Feb 1;173(2):511–514. doi: 10.1084/jem.173.2.511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Robinson W. E., Jr, Montefiori D. C., Gillespie D. H., Mitchell W. M. Complement-mediated, antibody-dependent enhancement of HIV-1 infection in vitro is characterized by increased protein and RNA syntheses and infectious virus release. J Acquir Immune Defic Syndr. 1989;2(1):33–42. [PubMed] [Google Scholar]
  28. Rollins S. A., Zhao J., Ninomiya H., Sims P. J. Inhibition of homologous complement by CD59 is mediated by a species-selective recognition conferred through binding to C8 within C5b-8 or C9 within C5b-9. J Immunol. 1991 Apr 1;146(7):2345–2351. [PubMed] [Google Scholar]
  29. Rooney I. A., Atkinson J. P., Krul E. S., Schonfeld G., Polakoski K., Saffitz J. E., Morgan B. P. Physiologic relevance of the membrane attack complex inhibitory protein CD59 in human seminal plasma: CD59 is present on extracellular organelles (prostasomes), binds cell membranes, and inhibits complement-mediated lysis. J Exp Med. 1993 May 1;177(5):1409–1420. doi: 10.1084/jem.177.5.1409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Saifuddin M., Ghassemi M., Patki C., Parker C. J., Spear G. T. Host cell components affect the sensitivity of HIV type 1 to complement-mediated virolysis. AIDS Res Hum Retroviruses. 1994 Jul;10(7):829–837. doi: 10.1089/aid.1994.10.829. [DOI] [PubMed] [Google Scholar]
  31. Schols D., Pauwels R., Desmyter J., De Clercq E. Presence of class II histocompatibility DR proteins on the envelope of human immunodeficiency virus demonstrated by FACS analysis. Virology. 1992 Jul;189(1):374–376. doi: 10.1016/0042-6822(92)90719-6. [DOI] [PubMed] [Google Scholar]
  32. Seya T., Atkinson J. P. Functional properties of membrane cofactor protein of complement. Biochem J. 1989 Dec 1;264(2):581–588. doi: 10.1042/bj2640581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Spear G. T., Sullivan B. L., Landay A. L., Lint T. F. Neutralization of human immunodeficiency virus type 1 by complement occurs by viral lysis. J Virol. 1990 Dec;64(12):5869–5873. doi: 10.1128/jvi.64.12.5869-5873.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Spear G. T., Takefman D. M., Sullivan B. L., Landay A. L., Zolla-Pazner S. Complement activation by human monoclonal antibodies to human immunodeficiency virus. J Virol. 1993 Jan;67(1):53–59. doi: 10.1128/jvi.67.1.53-59.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Wei X., Ghosh S. K., Taylor M. E., Johnson V. A., Emini E. A., Deutsch P., Lifson J. D., Bonhoeffer S., Nowak M. A., Hahn B. H. Viral dynamics in human immunodeficiency virus type 1 infection. Nature. 1995 Jan 12;373(6510):117–122. doi: 10.1038/373117a0. [DOI] [PubMed] [Google Scholar]
  36. Welsh R. M., Jr, Cooper N. R., Jensen F. C., Oldstone M. B. Human serum lyses RNA tumour viruses. Nature. 1975 Oct 16;257(5527):612–614. doi: 10.1038/257612a0. [DOI] [PubMed] [Google Scholar]
  37. White R. V., Kaufman K. M., Letson C. S., Platteborze P. L., Sodetz J. M. Characterization of rabbit complement component C8. Functional evidence for the species-selective recognition of C8 alpha by homologous restriction factor (CD59). J Immunol. 1994 Mar 1;152(5):2501–2508. [PubMed] [Google Scholar]
  38. Wilcox L. A., Ezzell J. L., Bernshaw N. J., Parker C. J. Molecular basis of the enhanced susceptibility of the erythrocytes of paroxysmal nocturnal hemoglobinuria to hemolysis in acidified serum. Blood. 1991 Aug 1;78(3):820–829. [PubMed] [Google Scholar]
  39. Wing M. G., Zajicek J., Seilly D. J., Compston D. A., Lachmann P. J. Oligodendrocytes lack glycolipid anchored proteins which protect them against complement lysis. Restoration of resistance to lysis by incorporation of CD59. Immunology. 1992 May;76(1):140–145. [PMC free article] [PubMed] [Google Scholar]
  40. Yoshida M., Miyoshi I., Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031–2035. doi: 10.1073/pnas.79.6.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. van den Berg C. W., Williams O. M., Morgan B. P. Presence of a dysfunctional form of CD59 on a CD59+ subclone of the U937 cell line. Immunology. 1994 Apr;81(4):637–642. [PMC free article] [PubMed] [Google Scholar]

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