Inhibition of HIV replication by pokeweed antiviral protein targeted to CD4+ cells by monoclonal antibodies

• Published in: Nature (London) Vol. 347; no. 6288; pp. 92 - 95
• Main Authors: Zarling, J.M, Moran, P.A, Haffar, O, Sias, J, Richman, D.D, Spina, C.A, Myers, D.E, Kuebelbeck, V, Ledbetter, J.A, Uckun, F.M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 06.09.1990; Nature Publishing Group
• Subjects: Acquired immune deficiency syndrome; AIDS; Antibodies, Monoclonal; Antigens; Antigens, CD - immunology; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacology; Biological and medical sciences; Bone growth; Bone marrow; CD4 antigen; CD4 Antigens - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - microbiology; Cell proliferation; Cells (biology); Conjugates; Depletion; Flowers & plants; Fundamental and applied biological sciences. Psychology; HIV; HIV-1 - drug effects; HIV-1 - physiology; Human immunodeficiency virus; Humans; Immunoglobulins; Immunotoxins; Infections; inhibition; leaves; Lymphocytes; Lymphocytes T; Medical research; Microbiology; Monoclonal antibodies; N-Glycosyl Hydrolases; Osteoprogenitor cells; Phytolacca americana; Plant Proteins - administration & dosage; Plant Proteins - pharmacology; Pokeweed antiviral protein; Protein synthesis; Proteins; replication; Ribosome Inactivating Proteins, Type 1; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Virology; Virus Replication - drug effects; Viruses; Human; Virus multiplication; HIV-1 virus; Retroviridae; Monoclonal antibody; Virus; Proteins; Dicotyledones; Angiospermae; T-Lymphocyte; Lentivirinae; Antiviral; Replication; Spermatophyta; Human immunodeficiency virus; Inhibition; Conjugated compound; Phytolaccaceae
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/347092a0

Functional impairment and selective depletion of CD4+ T cells, the hallmark of AIDS, are at least partly caused by human immunodeficiency virus (HIV-1) type I binding to the CD4 molecule and infecting CD4+ cells. It may, therefore, be of therapeutic value to target an target an antiviral agent to CD4+ cells to prevent infection and and to inhibit HIV-1 production in patients' CD4+ cells which contain proviral DNA. We report here that HIV-1 replication in normal primary, CD4+ T cells can be inhibited by pokeweed antiviral protein, a plant protein of relative molecular mass 30,000, which inhibits replication of certain plant RNA viruses, and of herpes simplex virus, poliovirus and influenza virus. Targeting pokeweed antiviral protein to CD4+ T cells by conjugating it to monoclonal antibodies reactive with CD5, CD7 or CD4 expressed on CD4+ cells, increased its anti-HIV potency up to 1,000-fold. HIV-1 replication is inhibited at picomolar concentrations of conjugates of pokeweed antiviral protein and monoclonal antibodies, which do not inhibit proliferation of normal CD4+ T cells or CD4-dependent responses. These conjugates inhibit HIV-1 protein synthesis and also strongly inhibit HIV-1 production in activated CD4+ T cells from infected patients.