Evaluation of anti-human immunodeficiency virus effect of recombinant CD4-immunoglobulin in vitro: a good candidate for AIDS treatment.
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.
Chowdhury
I H
IH
Department of Microbiology, Tokyo Medical and Dental University School of Medicine, Japan.
Koyanagi
Y
Y
Takamatsu
K
K
Yoshida
O
O
Kobayashi
S
S
Yamamoto
N
N
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D015704:CD4 Antigens / Q000008:administration & dosage* / Q000627:therapeutic use; D002459:Cell Fusion; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D005069:Evaluation Studies as Topic; D006678:HIV; D015658:HIV Infections / Q000628:therapy*; D006207:Half-Life; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D009000:Monocytes / Q000382:microbiology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000382:microbiology
D015704:CD4 Antigens; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins