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. 1996 Jan 1;183(1):307–310. doi: 10.1084/jem.183.1.307

Efficient destruction of human immunodeficiency virus in human serum by inhibiting the protective action of complement factor H and decay accelerating factor (DAF, CD55)

PMCID: PMC2192395  PMID: 8551237

Abstract

Activation of the human complement system leads to complement deposition on human immunodeficiency virus (HIV) and HIV-infected cells without causing efficient complement-mediated lysis. Even in the presence of HIV-specific antibodies, only a few particles are destroyed, demonstrating that HIV is intrinsically resistant to human complement. Here we report that, in addition to decay accelerating factor (DAF) being partially responsible, human complement factor H (CFH), a humoral negative regulator of complement activation, is most critical for this resistance. In the presence of HIV-specific antibodies, sera devoid of CFH (total genetic deficiency or normal human serum depleted of CFH by affinity chromatography) lysed free virus and HIV-infected but not uninfected cells. In the presence of CFH, lysis of HIV was only obtained when binding of CFH to gp41 was inhibited by a monoclonal antibody against a main CFH-binding site in gp41. Since CFH is an abundant protein in serum, and high local concentration of CFH can be obtained at the surface of HIV as the result of specific interactions of CFH with the HIV envelope, it is proposed that the resistance of HIV and HIV-infected cells against complement-mediated lysis in vivo is dependent on DAF and CFH and can be overcome by suppressing this protection. Neutralization of HIV may be achieved by antibodies against DAF and, more importantly, antibodies against CFH-binding sites on HIV envelope proteins.

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Selected References

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  1. 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]
  2. 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]
  3. Dierich M. P., Ebenbichler C. F., Marschang P., Füst G., Thielens N. M., Arlaud G. J. HIV and human complement: mechanisms of interaction and biological implication. Immunol Today. 1993 Sep;14(9):435–440. doi: 10.1016/0167-5699(93)90246-H. [DOI] [PubMed] [Google Scholar]
  4. Ezekowitz R. A., Kuhlman M., Groopman J. E., Byrn R. A. A human serum mannose-binding protein inhibits in vitro infection by the human immunodeficiency virus. J Exp Med. 1989 Jan 1;169(1):185–196. doi: 10.1084/jem.169.1.185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Folks T. M., Powell D., Lightfoote M., Koenig S., Fauci A. S., Benn S., Rabson A., Daugherty D., Gendelman H. E., Hoggan M. D. Biological and biochemical characterization of a cloned Leu-3- cell surviving infection with the acquired immune deficiency syndrome retrovirus. J Exp Med. 1986 Jul 1;164(1):280–290. doi: 10.1084/jem.164.1.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Horstmann R. D., Sievertsen H. J., Knobloch J., Fischetti V. A. Antiphagocytic activity of streptococcal M protein: selective binding of complement control protein factor H. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1657–1661. doi: 10.1073/pnas.85.5.1657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Marschang P., Sodroski J., Würzner R., Dierich M. P. Decay-accelerating factor (CD55) protects human immunodeficiency virus type 1 from inactivation by human complement. Eur J Immunol. 1995 Jan;25(1):285–290. doi: 10.1002/eji.1830250147. [DOI] [PubMed] [Google Scholar]
  8. Muster T., Guinea R., Trkola A., Purtscher M., Klima A., Steindl F., Palese P., Katinger H. Cross-neutralizing activity against divergent human immunodeficiency virus type 1 isolates induced by the gp41 sequence ELDKWAS. J Virol. 1994 Jun;68(6):4031–4034. doi: 10.1128/jvi.68.6.4031-4034.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Pangburn M. K., Schreiber R. D., Müller-Eberhard H. J. Formation of the initial C3 convertase of the alternative complement pathway. Acquisition of C3b-like activities by spontaneous hydrolysis of the putative thioester in native C3. J Exp Med. 1981 Sep 1;154(3):856–867. doi: 10.1084/jem.154.3.856. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Pintér C., Siccardi A. G., Longhi R., Clivio A. Direct interaction of complement factor H with the C1 domain of HIV type 1 glycoprotein 120. AIDS Res Hum Retroviruses. 1995 May;11(5):577–588. doi: 10.1089/aid.1995.11.577. [DOI] [PubMed] [Google Scholar]
  11. Pintér C., Siccardi A. G., Lopalco L., Longhi R., Clivio A. HIV glycoprotein 41 and complement factor H interact with each other and share functional as well as antigenic homology. AIDS Res Hum Retroviruses. 1995 Aug;11(8):971–980. doi: 10.1089/aid.1995.11.971. [DOI] [PubMed] [Google Scholar]
  12. Reisinger E. C., Vogetseder W., Berzow D., Köfler D., Bitterlich G., Lehr H. A., Wachter H., Dierich M. P. Complement-mediated enhancement of HIV-1 infection of the monoblastoid cell line U937. AIDS. 1990 Oct;4(10):961–965. doi: 10.1097/00002030-199010000-00003. [DOI] [PubMed] [Google Scholar]
  13. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet. 1988 Apr 9;1(8589):790–794. doi: 10.1016/s0140-6736(88)91657-1. [DOI] [PubMed] [Google Scholar]
  14. Saifuddin M., Parker C. J., Peeples M. E., Gorny M. K., Zolla-Pazner S., Ghassemi M., Rooney I. A., Atkinson J. P., Spear G. T. Role of virion-associated glycosylphosphatidylinositol-linked proteins CD55 and CD59 in complement resistance of cell line-derived and primary isolates of HIV-1. J Exp Med. 1995 Aug 1;182(2):501–509. doi: 10.1084/jem.182.2.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Soelder B. M., Reisinger E. C., Koefler D., Bitterlich G., Wachter H., Dierich M. P. Complement receptors: another port of entry for HIV. Lancet. 1989 Jul 29;2(8657):271–272. doi: 10.1016/s0140-6736(89)90452-2. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Spear G. T., Sullivan B. L., Takefman D. M., Landay A. L., Lint T. F. Human immunodeficiency virus (HIV)-infected cells and free virus directly activate the classical complement pathway in rabbit, mouse and guinea-pig sera; activation results in virus neutralization by virolysis. Immunology. 1991 Aug;73(4):377–382. [PMC free article] [PubMed] [Google Scholar]
  18. Stoiber H., Ebenbichler C., Schneider R., Janatova J., Dierich M. P. Interaction of several complement proteins with gp120 and gp41, the two envelope glycoproteins of HIV-1. AIDS. 1995 Jan;9(1):19–26. doi: 10.1097/00002030-199501000-00003. [DOI] [PubMed] [Google Scholar]
  19. Stoiber H., Schneider R., Janatova J., Dierich M. P. Human complement proteins C3b, C4b, factor H and properdin react with specific sites in gp120 and gp41, the envelope proteins of HIV-1. Immunobiology. 1995 Jun;193(1):98–113. doi: 10.1016/s0171-2985(11)80158-0. [DOI] [PubMed] [Google Scholar]
  20. Stoiber H., Thielens N. M., Ebenbichler C., Arlaud G. J., Dierich M. P. The envelope glycoprotein of HIV-1 gp120 and human complement protein C1q bind to the same peptides derived from three different regions of gp41, the transmembrane glycoprotein of HIV-1, and share antigenic homology. Eur J Immunol. 1994 Feb;24(2):294–300. doi: 10.1002/eji.1830240203. [DOI] [PubMed] [Google Scholar]
  21. Tremblay M., Meloche S., Sekaly R. P., Wainberg M. A. Complement receptor 2 mediates enhancement of human immunodeficiency virus 1 infection in Epstein-Barr virus-carrying B cells. J Exp Med. 1990 May 1;171(5):1791–1796. doi: 10.1084/jem.171.5.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Weiler J. M., Daha M. R., Austen K. F., Fearon D. T. Control of the amplification convertase of complement by the plasma protein beta1H. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3268–3272. doi: 10.1073/pnas.73.9.3268. [DOI] [PMC free article] [PubMed] [Google Scholar]

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