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

doi:10.1084/jem.183.1.307

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Stoiber, H.
	Articles by Dierich, M. P.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Stoiber, H.
	Articles by Dierich, M. P.


Social Bookmarking

	What's this?

ARTICLES

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

H Stoiber, C Pinter, AG Siccardi, A Clivio and MP Dierich
Institut fur Hygiene, Ludwig Boltzmann Institut fur AIDS Forschung, Innsbruck, Austria.

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.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Huber, M., von Wyl, V., Ammann, C. G., Kuster, H., Stiegler, G., Katinger, H., Weber, R., Fischer, M., Stoiber, H., Gunthard, H. F., Trkola, A. (2008). Potent Human Immunodeficiency Virus-Neutralizing and Complement Lysis Activities of Antibodies Are Not Obligatorily Linked. J. Virol. 82: 3834-3842 [Abstract] [Full Text]
Aasa-Chapman, M. M. I., Holuigue, S., Aubin, K., Wong, M., Jones, N. A., Cornforth, D., Pellegrino, P., Newton, P., Williams, I., Borrow, P., McKnight, A. (2005). Detection of Antibody-Dependent Complement-Mediated Inactivation of both Autologous and Heterologous Virus in Primary Human Immunodeficiency Virus Type 1 Infection. J. Virol. 79: 2823-2830 [Abstract] [Full Text]
Horakova, E., Gasser, O., Sadallah, S., Inal, J. M., Bourgeois, G., Ziekau, I., Klimkait, T., Schifferli, J. A. (2004). Complement Mediates the Binding of HIV to Erythrocytes. J. Immunol. 173: 4236-4241 [Abstract] [Full Text]
Gould, S. J., Booth, A. M., Hildreth, J. E. K. (2003). The Trojan exosome hypothesis. Proc. Natl. Acad. Sci. USA 100: 10592-10597 [Abstract] [Full Text]
Wolbank, S., Kunert, R., Stiegler, G., Katinger, H. (2003). Characterization of Human Class-Switched Polymeric (Immunoglobulin M [IgM] and IgA) Anti-Human Immunodeficiency Virus Type 1 Antibodies 2F5 and 2G12. J. Virol. 77: 4095-4103 [Abstract] [Full Text]
Bouhlal, H., Chomont, N., Haeffner-Cavaillon, N., Kazatchkine, M. D., Belec, L., Hocini, H. (2002). Opsonization of HIV-1 by Semen Complement Enhances Infection of Human Epithelial Cells. J. Immunol. 169: 3301-3306 [Abstract] [Full Text]
Takefman, D. M., Spear, G. T., Saifuddin, M., Wilson, C. A. (2002). Human CD59 Incorporation into Porcine Endogenous Retrovirus Particles: Implications for the Use of Transgenic Pigs for Xenotransplantation. J. Virol. 76: 1999-2002 [Abstract] [Full Text]
Moghimi, S. M., Hunter, A. C., Murray, J. C. (2001). Long-Circulating and Target-Specific Nanoparticles: Theory to Practice. Pharmacol. Rev. 53: 283-318 [Abstract] [Full Text]
Alfsen, A., Iniguez, P., Bouguyon, E., Bomsel, M. (2001). Secretory IgA Specific for a Conserved Epitope on gp41 Envelope Glycoprotein Inhibits Epithelial Transcytosis of HIV-1. J. Immunol. 166: 6257-6265 [Abstract] [Full Text]
Tacnet-Delorme, P., Boyer, V., Thielens, N. M., Hernandez, J.-F., Bally, I., Sim, R. B., Desgranges, C., Arlaud, G. J. (1999). In Vitro Analysis of Complement-Dependent HIV-1 Cell Infection Using a Model System. J. Immunol. 162: 4088-4093 [Abstract] [Full Text]
Yamada, A., Kubo, K., Takeshita, T., Harashima, N., Kawano, K., Mine, T., Sagawa, K., Sugamura, K., Itoh, K. (1999). Molecular Cloning of a Glycosylphosphatidylinositol-Anchored Molecule CDw108. J. Immunol. 162: 4094-4100 [Abstract] [Full Text]
Ram, S., Sharma, A. K., Simpson, S. D., Gulati, S., McQuillen, D. P., Pangburn, M. K., Rice, P. A. (1998). A Novel Sialic Acid Binding Site on Factor H Mediates Serum Resistance of Sialylated Neisseria gonorrhoeae. J. Exp. Med. 187: 743-752 [Abstract] [Full Text]
Richardson, J., Moraillon, A., Crespeau, F., Baud, S., Sonigo, P., Pancino, G. (1998). Delayed Infection after Immunization with a Peptide from the Transmembrane Glycoprotein of the Feline Immunodeficiency Virus. J. Virol. 72: 2406-2415 [Abstract] [Full Text]