Two parallel routes of the complement-mediated antibody-dependent enhancement of HIV-1 infection.
OBJECTIVE
To study the mechanism of the complement-mediated antibody-dependent enhancement (C'-ADE) of HIV infection which may play a significant role in the progression of HIV-disease.


METHODS
In vitro complement activating and complement-mediated HIV-infection enhancing abilities of three human anti-gp41 monoclonal antibodies (MAb) were tested. C'-ADE was estimated using HIV-1IIIB and CR2 (CD21)-carrying MT-4 target cells. Normal human serum (NHS), purified C1q, C1q-deficient (C1qD) and C2-deficient (C2D) human sera were applied as complement sources.


RESULTS
All MAb mediated increased C1q binding to solid-phase gp41. All MAb had a marked dose-dependent and strictly complement-mediated HIV-infection enhancing effect. Mixtures of the MAb with purified C1q also significantly increased HIV-1 infection. C1qD serum had a markedly lower enhancing effect than NHS, which could be raised to normal level by addition of purified C1q. Pretreatment of the target cells with anti-CR2 antibodies only partially inhibited the enhancing effect of the MAb plus normal human serum.


CONCLUSIONS
These novel findings indicate that besides the well-known facilitation of entry of HIV-1 by the interaction between virus-bound C3 fragments and CR2 present on the target cells, fixation of C1q to intact virions also results in an enhanced productive HIV-1 infection in the MT-4 cell cultures.
Prohászka
Z
Z
National Institute of Haematology, Blood Transfusion and Immunology, Budapest, Hungary.
Nemes
J
J
Hidvégi
T
T
Tóth
F D
FD
Kerekes
K
K
Erdei
A
A
Szabó
J
J
Ujhelyi
E
E
Thielens
N
N
Dierich
M P
MP
Späth
P
P
Ghebrehiwet
B
B
Hampl
H
H
Kiss
J
J
Arlaud
G
G
Füst
G
G
D000911:Antibodies, Monoclonal / Q000276:immunology; D015922:Complement C1q / Q000276:immunology* / Q000494:pharmacology; D018450:Disease Progression; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000503:physiopathology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D015922:Complement C1q