Soluble gC1q-R/p33, a cell protein that binds to the globular "heads" of C1q, effectively inhibits the growth of HIV-1 strains in cell cultures

C1q and the outer envelope protein of HIV, gp120, have several structural a nd functional similarities. Therefore, it is plausible to assume that prote ins that are able to interact with C1q may also interact with isolated gp12 0 as well as the whole HIV-1 virus. Based on this hypothesis, we studied th e potential ability of the recombinant form of the 33-kDa protein, which bi nds to the globular "heads" of Clq (gC1q-R/p33), to inhibit the growth of d ifferent HIV-1 strains in cell cultures, gC1q-R/p33 was found to effectivel y and dose-dependently inhibit the production of one T-lymphotropic (X4) an d one macrophage-tropic (R5) strain in human T cell lines (MT-4 and H9) and human monocyte-derived macrophage cultures, respectively, At a concentrati on range of 5-25 mug/ml, gC1q-R caused a marked and prolonged suppression o f virus production. The extent of inhibition was enhanced when gC1q-R was f irst incubated with and then removed from the target cell cultures before v irus infection, compared to that when the cells were infected with gC1q-R-H IV mixtures. The extent of inhibition was comparable to that of the Leu3a a nti-CD4 antibody. Addition of gC1q-R to the cell cultures on day 1 or 2 aft er infection induced markedly less inhibition of HIV-1 growth than pretreat ment of the cells just before or together with the infective HIV strains. I n ELISA experiments, gC1q-R did not bind to a solid-phase recombinant gp120 while strong and dose-dependent binding of gC1q-R to solid-phase CD4 was o bserved. Our present findings indicate that gC1q-R is an effective inhibito r of HIV-1 infection, which prevents viral entry by blocking the interactio n between CD4 and gp120, Since gC1q-R is a human protein, it is most probab ly not antigenic in humans. It would seem logical, therefore, to consider g C1q-R or its fragments involved in the CD4 binding as potential therapeutic agents. (C) 2001 Acaaemic Press.