Soluble glycosaminoglycans do not potentiate RANTES antiviral activity on the infection of primary macrophages by human immunodeficiency virus type 1

Macrophages play an important role in human immunodeficiency virus (HIV)-1 infection. They exist in various differentiation and activation states in v ivo, a heterogeneity that may affect their interactions with HIV-1 and susc eptibility to drugs. Here, we found that RANTES and MIP-1 beta, heparin, or soluble chondroitin sulfate B, but not chondroitin sulfate A, inhibited HI V-1(BaL) infection of macrophages obtained as the adherent cells of 5-day c ultures of blood mononuclear cells (PBMC), followed by 2 days without eithe r nonadherent PBMC or added cytokines (MDM-5d), whereas they did not affect infection of macrophages obtained as the adherent cells recovered from I-h incubation of PBMC and subsequent 7-day culture with macrophage colony-sti mulating factor (MDM-MCSF). Such different behavior was not related to diff erences in HIV-I binding but rather to postbinding steps, as HIV-1(BaL) att ached similarly to MDM-5d and MDM-MCSF, a binding that was affected by solu ble glycosaminoglycans but not by RANTES. Of note, CCR5 expression on both types of MDM was comparable. and it was not downregulated by RANTES on eith er. Mixing RANTES with each of the glycosaminoglycans did not restore inhib ition of MDM-MCSF infection by HIV-1; however, heparin at concentrations th at had low antiviral activity for MDM-5d counteracted RANTES anti-HIV-l act ivity for these cells, whereas chondroitin sulfate B had no additive effect on that of RANTES. Both glycosaminoglycans affected RANTES binding to MDM. Thus, in contrast to cell surface proteoglycans that contribute to the att achment of RANTES to macrophages and enhance its anti-HIV-l activity, solub le glycosaminoglycans do not facilitate, and may even offset. the anti-HIV- l activity of RANTES. (C) 2000 Academic Press.