Characterization and anti-HIV properties of CD 4-coated red blood cells

Abstract

Entry of HIV into its target cells requires its binding to the CD 4 molecule, the HIV receptor. Blocking this initial step of HIV life cycle is a potential target for the design of anti-HIV drugs. Soluble recombinant CD 4 efficiently blocks HIV infection in vitro and is the least toxic anti-HIV drug in humans. However, this molecule has a short half-life in vivo, and poorly neutralizes fresh isolates of HIV-1. Modifications of soluble CD 4 have been constructed, aimed at increasing its half life and other anti-viral properties. We have previously described an efficient method to cross-link soluble CD 4 to human red blood cells. We show here that these cells are uniformly coated as observed by immunofluorescence staining. Each of 8 different anti-CD 4 monoclonal antibodies stained these cells indicating that the epitopes recognized by these antibodies are correctly exposed at the cell membrane. These CD 4-expressing RBC inhibit specifically and in a dose dependent manner the HIV binding to, and infection of, CD 4+ target cells. On a CD 4 molar basis, this inhibition is approximately 15 times more efficient with CD 4-coated red blood cells than with soluble CD 4.