Ribosomal inhibitory proteins from plants inhibit HIV-1 replication in acutely infected peripheral blood mononuclear cells.
Peripheral blood mononuclear cells from seronegative donors were stimulated with phytohemagglutinin and then infected with human immunodeficiency virus (HIV-1). Using this experimental system, the antiviral activity of two translation inhibitory proteins (pokeweed antiviral protein, PAP-S, and Luffa ribosomal inhibitory protein, LRIP-I) isolated from plants and a recombinant form of ricin A chain were studied. Previously, it had been shown that toxin polypeptides linked to monoclonal antibodies could inhibit HIV-infected cells. In the present study, the free, unconjugated, proteins were found to inhibit HIV replication at doses in which they were nontoxic to uninfected peripheral blood mononuclear cells. Among the inhibitory proteins, PAP-S and recombinant ricin A chain markedly reduced the reverse transcriptase activity and the expression of p24 core protein in infected cultures. Dose response studies indicate that the anti-HIV activity of PAP-S was comparable to AZT. The other ribosome inhibitory proteins (RIPs) showed moderate but significant antiviral activity.
Olson
M C
MC
Department of Pharmacology, University of Minnesota, Minneapolis 55455.
Ramakrishnan
S
S
Anand
R
R
D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000382:microbiology*; D009699:N-Glycosyl Hydrolases; D010940:Plant Proteins / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D012276:Ricin; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology
C074465:LRIP-I protein, Luffa cylindrica; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D015215:Zidovudine; D012276:Ricin; D054303:HIV Reverse Transcriptase; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein