Potent inhibition of human immunodeficiency virus type 1 replication by an intracellular anti-Rev single-chain antibody.
Human immunodeficiency virus type 1 (HIV-1) has a complex life cycle, which has made it a difficult target for conventional therapeutic modalities. A single-chain antibody moiety, directed against the HIV-1 regulatory protein Rev, which rescues unspliced viral RNA from the nucleus of infected cells, has now been developed. This anti-Rev single-chain construct (SFv) consists of both light and heavy chain variable regions of anti-Rev monoclonal antibody, which, when expressed intracellularly within human cells, potently inhibits HIV-1 replication. This intracellular SFv molecule is demonstrated to specifically antagonize Rev function. Thus, intracellular SFv expression, against a retroviral regulatory protein, may be useful as a gene therapeutic approach to combat HIV-1 infections.
Duan
L
L
Dorrance H. Hamilton Laboratories, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Bagasra
O
O
Laughlin
M A
MA
Oakes
J W
JW
Pomerantz
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents; D015152:Blotting, Northern; D005455:Fluorescent Antibody Technique; D015694:Gene Products, rev / Q000276:immunology*; D015483:HIV Antibodies / Q000235:genetics / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D014162:Transfection; D014779:Virus Replication; D054321:rev Gene Products, Human Immunodeficiency Virus
D000998:Antiviral Agents; D015694:Gene Products, rev; D015483:HIV Antibodies; D054321:rev Gene Products, Human Immunodeficiency Virus