Mechanism of injury of virus-infected cells by antiviral antibody and complement: participation of IgG, F(ab')2, and the alternative complement pathway.

Abstract

Antibody-mediated C-dependent lysis of cell lines infected with herpes simplex type 1 virus, influenza A degrees virus, measles virus, and mumps virus occurred by the alternative C pathway with the participation of IgG antibodies. Lysis occurred only with immune human sera, Mg++ EGTA immune sera, and immune sera depleted of C4 or treated with Fab anti-C4. Lysis did not occur with nonimmune sera, Mg++ EDTA immune sera, and immune sera heated 50 degrees C for 25 min, depleted of factor B or treated with Fab antifactor B. Lysis was restored to heated and factor B immunodepleted immune sera by addition of factor B, but not by addition of an excess of C2. Further studies showed that lysis of HeLa cells infected with measles virus was induced by both immune IgG and F(ab')2 but not Fab' in the presence of a nonantibody-containing human C source. Lysis of measles virus-infected cells was also indpendent of movement of viral antigens on the surface of the infected cells, as inhibition of viral antigen capping by cytochalasin B or sodium azide was not associated with abrogation of immune lysis.

Lysis of measles virus-infected cells by the purified cytolytic alternative complement pathway and antibody.

“…The fact that both IgG and F(ab')2 fragments of measles antibody-induced lysis extends previous findings (2) by showing that IgG and F(ab')2 are equally effective on a molecular basis in inducing lysis over a range of doses. Moreover, an equivalent amount of Fab' bound to the infected cell was totally ineffective in inducing lysis.…”

“…the above experiments and in previous studies (1,2); maximum 51Cr release correlated with morphological cell death. Kinetic studies showed that lysis of infected cells coated with IgG began at 30 min and was maximal by 60-90 min.…”

“…In initial studies, lysis was assessed by the eosin microcytotoxicity assay as in previous studies (1,2). A small-scale SlCr-release assay was developed to facilitate quantitation of lysis while still enabling the use of small volumes of reagents.…”

Homozygous C2 deficiency with fulminant lupus erythematosus. severe nephritis via the alternative complement pathway

“…It is now clear that cytocidal activity can be initiated upon activation of the alternative C pathway both at the cell surface (20,(53)(54)(55)(56) and in solution (25)(26)(27). Activation of this pathway can result in the generation of anaphylatoxins and neutrophil chemotactic factors from C3 and/or C5 and in cytolysis by mechanisms involving either the formation of a C3 convertase at the cell surface or the attachment of C m to bystander cells independent of the presence of C3 with enhancement of such lysis when C3 is present (5738).…”

Complement‐Dependent Cytotoxicity of Sera Obtained from Subacute Sclerosing Panencephalitis Patients

“…CL50 for NC-Mantooth cells differed from that for the other cell lines. Perrin et al (8) proposed that complement-dependent cytolysis of measles virus-infected cells was mediated by the alternative complement pathway. The results of complement requirement in this study suggest that the complement pathway related to the complement-dependent cytolysis might be dependent on the virus strain persistently infecting NC-37 cells.…”