Activation of complement on the surface of cells infected by human immunodeficiency virus.
Cells were infected with HIV-1 and tested for C activation using a flow cytometric assay for bound C3 fragments. HIV-infected H9 cells bound increased levels of C3 using normal human serum as a C source only after cells were first incubated with serum containing anti-HIV antibody. Uninfected H9 cells or infected cells incubated with HIV-antibody negative sera did not bind C3. Although C3 bound quickly and was maximal within 10 min, modulation of bound C3 was slow with about 50% loss after 4 h. C3 binding required specific anti-HIV antibody, was blocked by EGTA, and did not occur in C2-deficient serum suggesting that binding was via the classical pathway. The HTLV-1-infected MT-4 cell line also bound high levels of C3 after coinfection with HIV. C3 binding in HIV-infected MT4 cells was also mediated via the classical pathway because it was not observed in Mg-EGTA chelated or C2-deficient sera. However, this classical pathway activation appeared to be antibody independent because it was also detected in HIV-antibody negative serum and a-gamma-globulinemic serum. This indicates that coinfection with HTLV-1 and HIV-1 can produce novel C activating conditions. No cytotoxic effect of human C for antibody-treated HIV-infected cells was observed in a chromium release assay. However, rabbit C was cytotoxic for HIV-infected cells in the absence of anti-HIV antibodies. Our results suggest that C can be activated in vivo by infected cells via specific anti-HIV antibody. The resultant C3 deposition on infected cells could have profound effects on interaction with CR-bearing cells.
Spear
G T
GT
Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612.
Landay
A L
AL
Sullivan
B L
BL
Dittel
B
B
Lint
T F
TF
D000920:Antibody-Dependent Cell Cytotoxicity; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism*; D003171:Complement Pathway, Classical; D003602:Cytotoxicity, Immunologic; D006800:Deltaretrovirus Infections / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D009175:Mycoplasma Infections / Q000276:immunology
D003176:Complement C3; D015483:HIV Antibodies