Complement activation by HIV-1-infected cells: the role of transmembrane glycoprotein gp41.
To characterize the mechanisms of complement activation by human immunodeficiency virus type 1 (HIV-1)-infected cells, Cl-4 cells stably expressing the envelope glycoproteins of HIV-1 and the parent African green monkey cell line CV-1 were tested for C1q binding and complement activation. While the parent cell line CV-1 only showed a weak spontaneous activation of the alternative pathway, Cl-4 cells additionally triggered the classical pathway of complement activation independent of anti-HIV antibodies by direct C1q binding. Earlier studies had shown different complement activating potential of cells infected with various HIV isolates. Recombinant soluble CD4-induced shedding of gp120 from the surface of HIV-1-infected cells converted a weak activator isolate (MVP-899) into a strong complement activator. The increase in complement activation was paralleled by the concomitant unmasking of a previously hidden gp41 epitope comprising the major complement-activating domain of gp41 (aa. 601-613). Our results strongly suggest that the transmembrane protein gp41 induces the activation of complement on the surface of infected cells as has been described previously for purified HIV-1 virions. Furthermore, we present evidence that the different potential of HIV isolates to activate the complement system on the cell surface is caused by different degrees of spontaneous gp120 shedding by various HIV isolates.
Marschang
P
P
Institut für Hygiene, Universität Innsbruck, Austria.
Krüger
U
U
Ochsenbauer
C
C
Gürtler
L
L
Hittmair
A
A
Bosch
V
V
Patsch
J R
JR
Dierich
M P
MP
D000818:Animals; D015153:Blotting, Western; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D002522:Chlorocebus aethiops; D003167:Complement Activation; D015922:Complement C1q / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism*; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D015700:HIV Envelope Protein gp41 / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D014162:Transfection
D015704:CD4 Antigens; D003176:Complement C3; D015700:HIV Envelope Protein gp41; D015922:Complement C1q