Properties and mechanism of action of a 17 amino acid, V3 loop-specific microantibody that binds to and neutralizes human immunodeficiency virus type1 virions

Only two virus-neutralizing peptide microantibodies (MicroAbs) have been de scribed and little is known about their mode of action. This report concern s a 17 amino acid cyclized MicroAb, derived from the third complementarity- determining region of the heavy chain of MAb F58 (IgG1), that recognizes th e same minimum epitope in the V3 loop of the gp120 envelope protein of huma n immunodeficiency virus type 1 (HIV-1) as the MAb, The MicroAb was able to bind to and neutralize free virus particles. It was up to 5-fold more effi cient in mass terms than F58 IgG and its neutralization rate on a molar bas is was only 32-fold lower. The mechanism of neutralization of the MicroAb w as also investigated. A high level of neutralization (99%) occurred without any significant decrease in attachment of virus to target C8166 cells. Neu tralized virus attached to CD4, the HIV-1 primary receptor. Fusion of virio ns to cells was partially inhibited by the MicroAb, whereas F58 IgG has bee n shown to inhibit fusion significantly. Thus, neutralization by the MicroA b appears to be mediated, at least in part, by inhibition of fusion. Contro l peptides, in which the tyrosine at position 5 or 6 was deleted or changed to phenylalanine, showed no antiviral activity, attesting to the specifici ty of interaction of the MicroAb with the virion. It therefore appears that the MicroAb acts like an immunoglobulin. The data also show that the Micro Ab/MAb F58 epitope on the V3 loop is not involved in attachment of virus to CD4 but is required for subsequent events in early infection.