EFFECT OF MANNOSYLATED DERIVATIVES ON HIV-1 INFECTION OF MACROPHAGES AND LYMPHOCYTES

We previously demonstrated that gp120/160 (Env) of HIV-1 interact in a carbohydrate-specific manner with mannosyl/-acetylglucosaminyl deriva tives and that HIV-1(LAI) infection of monocytic U937 and lymphoid CEM cells was inhibited by CD4-free Concanavalin A-reactive glycopeptides from U937 cells, We report here that the natural glycoproteins bovine fetuin and asialofetuin, human orosomucoid and alpha-fetoprotein, and mannan, which all specifically interact with Env, inhibited infection of primary macrophages by macrophage-tropic HIV-1 strains, whereas de xtran had no such effect, This activity was conserved if fetuin, asial ofetuin, or orosomucoid were heat-treated, which rules out the role of their three-dimensional structure, Orosomucoid and mannan partially i nhibited Env binding to macrophages but not to U937 or CEM cells, This indicates that Env does not bind in the same manner to primary macrop hages and to immortalized CD4(+) cells, and that orosomucoid and manna n act at CD4-independent stages of virus binding to macrophages. Manna n also inhibited Env binding to surface glycopeptides obtained after t rypsin treatment of macrophages, Furthermore, orosomucoid and fetuin i nteracted with, and they inhibited the binding of a V3 loop B clade co nsensus peptide to several macrophage membrane proteins, including two 36 and 42 kDa proteins, These data indicate that these glycoproteins interfere with post-binding events during HIV-1 infection of primary m acrophages. In contrast, the compounds did not affect infection of U93 7 or CEM cells by T-cell tropic HIV-1(LAI) nor infection of peripheral blood lymphocytes by HIV-1(LAI) or HIV-1(Ba-L). Thus, carbohydrate-sp ecific inhibition of HIV infection depends on the cell type more than on the viral strain, and differences in the glycan structure of cell-t ype-specific cofactors may be important for HIV entry into cells.