Evaluation of anti-human immunodeficiency virus effect of recombinant CD4-immunoglobulin in vitro: a good candidate for AIDS treatment

Abstract

CD4 molecule, a surface marker of helper T lymphocytes, interacts with gp120 of human immunodeficiency virus (HIV) with a high affinity and, hence, serves as a virus receptor. Soluble chimeric CD4-immunoglobulin (Ig) possesses anti-HIV activity due to its binding activity to gp120. Furthermore, this recombinant molecule has unique Ig-like properties representing Fc receptor-binding activity and a long half-life in vivo. In this report we have thoroughly evaluated the effect of this compound on HIV infection using different in vitro systems. Treatment with 4 micrograms/ml of recombinant CD4-Ig after infection completely blocked the HIV-specific cytopathic effect, antigen expression, and virus release in MT-4 cells, a human T cell line which is highly susceptible to HIV. Similarly, this molecule blocked the HTLV-III/B and YU-1 strains of HIV infection in peripheral blood mononuclear cells even at 1 microgram/ml. Pretreatment of the Fc receptor-positive cell line U937 with this reagent resulted not in enhancement but again in blocking of HIV infection. About 95% of HIV infection was inhibited in U937 cells when cells were treated with this compound at the time of exposure to HIV. Recombinant-CD4-Ig also completely inhibited HIV-induced syncytia formation between MOLT-4 and MOLT-4/HIV and resulting virus release at 8 and 2 micrograms/ml, respectively. Due to its stability and long half-life, this compound could be a promising therapeutic agent against HIV infection.