INTERACTION OF SEVERAL COMPLEMENT PROTEINS WITH GP120 AND GP41, THE 2ENVELOPE GLYCOPROTEINS OF HIV-1

Objective: To study the binding of human complement proteins to gp41 a nd gp120 of HIV-1. Methods: The interaction of complement proteins wit h gp41 and gp120 and their effect on the gp41-gp120 complex in enzyme- linked immunosorbent assays (ELISA) and on stably transfected Schneide r-2 cells expressing a gp41-gp120 complex was investigated. The molecu lar basis of these interactions was analysed by computer-supported seq uence analysis. Result: gp41 strongly binds human complement regulator y proteins factors H and properdin, and weakly binds factors I and B. The binding occurs with recombinant soluble (rs) gp41 fixed on ELISA p lates as well as gp41-gp120 complex expressed on Schneider-2 cells. Th e basis for this binding potential might be an amino-acid (aa) sequenc e of gp41 displaying homologies to sites in human C3. rgp120 also bind s C3(H2O), a C3b-like form of C3, and C4b. These binding features of g p120 can be explained by homology of constant region (CR) 4 in gp120 t o sites in C4b binding protein. Additionally, CR1 in gp120 exhibits a weak similarity to human properdin. Preincubation of rsgp41 with eithe r factor H or properdin, and of rgp120 with C3b or C4b affected the in teraction between rsgp41 and rgp120. Incubation of Schneider-2 cells, expressing a functional gp41-gp120 complex, with factor H reduced the detectable amount of gp120. This effect was similar to that induced by soluble CD4. Conclusion: These results strongly suggest that HIV-1 en velope proteins interact with human complement proteins. Additionally, C3b-like features of gp41 and the C3b/C4b binding structures in gp120 may affect the non-covalent association between gp41 and gp120.