Human immunodeficiency virus type 1 (HIV-1), in contrast to animal retroviruses such as murine leukemia virus, is not lysed by human complement. Nevertheless, HIV-1 activates complement via the classical pathway independent of antibody, and C3b deposition facilitates infection of complement receptor-bearing cells. Using gel exclusion chromatography on Sephacryl S-1000, purified virions were found to bind 125I-labeled C1q, but not 125I-labeled dimeric proenzyme C1s. Virions activated the C1 complex, reconstituted from C1q, proenzyme C1r, and 125I-labeled proenzyme C1s, to an extent comparable with that obtained with immunoglobulin G-ovalbumin immune complexes. To determine the activating viral component, recombinant viral proteins were used: in the solid phase, soluble gp41 (sgp41) (the outer membrane part of gp41, residues 539-684 of gp160) bound C1q, but not dimeric proenzyme C1s, while gp120 was ineffective. In the fluid phase, sgp41 activated the C1 complex in a dose- and time-dependent manner, more efficiently than aggregated Ig, but less efficiently than immune complexes. To localize the C1 activating site(s) in gp41, synthetic peptides (15-residue oligomers spanning amino acids 531-695 of gp160) were used. Peptides covering positions 591-605 and 601-620 and, to a lesser extent, positions 561-575, had both the ability to bind C1q and to induce C3 deposition. These data provide the first experimental evidence of a direct interaction between the C1 complex and HIV-1, and indicate that C1 binding and activation are mediated by specific sites in gp41.
Article|
December 01 1991
Human immunodeficiency virus type 1 activates the classical pathway of complement by direct C1 binding through specific sites in the transmembrane glycoprotein gp41.
C F Ebenbichler,
C F Ebenbichler
Institut für Hygiene, Innsbruck, Austria.
Search for other works by this author on:
N M Thielens,
N M Thielens
Institut für Hygiene, Innsbruck, Austria.
Search for other works by this author on:
R Vornhagen,
R Vornhagen
Institut für Hygiene, Innsbruck, Austria.
Search for other works by this author on:
P Marschang,
P Marschang
Institut für Hygiene, Innsbruck, Austria.
Search for other works by this author on:
G J Arlaud,
G J Arlaud
Institut für Hygiene, Innsbruck, Austria.
Search for other works by this author on:
M P Dierich
M P Dierich
Institut für Hygiene, Innsbruck, Austria.
Search for other works by this author on:
C F Ebenbichler
Institut für Hygiene, Innsbruck, Austria.
N M Thielens
Institut für Hygiene, Innsbruck, Austria.
R Vornhagen
Institut für Hygiene, Innsbruck, Austria.
P Marschang
Institut für Hygiene, Innsbruck, Austria.
G J Arlaud
Institut für Hygiene, Innsbruck, Austria.
M P Dierich
Institut für Hygiene, Innsbruck, Austria.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1991) 174 (6): 1417–1424.
Citation
C F Ebenbichler, N M Thielens, R Vornhagen, P Marschang, G J Arlaud, M P Dierich; Human immunodeficiency virus type 1 activates the classical pathway of complement by direct C1 binding through specific sites in the transmembrane glycoprotein gp41.. J Exp Med 1 December 1991; 174 (6): 1417–1424. doi: https://doi.org/10.1084/jem.174.6.1417
Download citation file: